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2.
Front Biosci (Landmark Ed) ; 23(8): 1407-1421, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29293442

ABSTRACT

Despite great progress in neuroscience, there are still fundamental unanswered questions about the brain, including the origin of subjective experience and consciousness. Some answers might rely on new physical mechanisms. Given that biophotons have been discovered in the brain, it is interesting to explore if neurons use photonic communication in addition to the well-studied electro-chemical signals. Such photonic communication in the brain would require waveguides. Here we review recent work (S. Kumar, K. Boone, J. Tuszynski, P. Barclay, and C. Simon, Scientific Reports 6, 36508 (2016)) suggesting that myelinated axons could serve as photonic waveguides. The light transmission in the myelinated axon was modeled, taking into account its realistic imperfections, and experiments were proposed both in vivo and in vitro to test this hypothesis. Potential implications for quantum biology are discussed.


Subject(s)
Axons/physiology , Brain/physiology , Nerve Fibers, Myelinated/physiology , Neurons/physiology , Animals , Axons/radiation effects , Brain/radiation effects , Humans , Light , Models, Neurological , Nerve Fibers, Myelinated/radiation effects , Neural Conduction/physiology , Neural Conduction/radiation effects , Neurons/radiation effects
3.
J Oral Maxillofac Surg ; 73(7): 1267-74, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25900233

ABSTRACT

PURPOSE: The aim of this study was to evaluate the relative effectiveness of stellate ganglion blockade (SGB) versus xenon light irradiation (XLI) for the treatment of neurosensory deficits resulting from orthognathic surgery as determined by a comparison of prospective measurements of electrical current perception thresholds (CPTs) and ranged CPTs (R-CPTs). MATERIALS AND METHODS: CPT and R-CPT in the mental foramen area were measured during electrical stimulation at 98 different sites on the body in patients who had undergone orthognathic surgery. After surgery, patients were assigned to the SGB group or the XLI group. CPT and R-CPT of the 2 groups were measured at stimulation frequencies of 2,000, 250, and 5 Hz before surgery, 1 week after surgery, and after 10 treatment sessions. Furthermore, the influence of surgical factors, such as genioplasty and a surgically exposed inferior alveolar nerve (IAN), was examined in the 2 groups. RESULTS: Patients' CPT and R-CPT values indicated a considerable amount of sensory disturbance in most cases after surgery. The change in magnitude of all CPT and R-CPT values for the SGB group decreased considerably compared with that for the XLI group after treatment. There was no correlation between CPT or R-CPT values and surgical factors (eg, genioplasty and exposure of the IAN). CONCLUSION: SGB of the IAN could be an effective method for treating neurosensory deficits after orthognathic surgery on the IAN.


Subject(s)
Lasers, Gas/therapeutic use , Low-Level Light Therapy/methods , Nerve Block/methods , Orthognathic Surgical Procedures/adverse effects , Postoperative Complications/therapy , Somatosensory Disorders/therapy , Stellate Ganglion/drug effects , Adolescent , Adult , Anesthetics, Local/administration & dosage , Electric Stimulation/methods , Female , Follow-Up Studies , Genioplasty/adverse effects , Humans , Male , Mandibular Nerve/drug effects , Mandibular Nerve/physiopathology , Mandibular Nerve/radiation effects , Maxilla/surgery , Mepivacaine/administration & dosage , Middle Aged , Nerve Fibers, Myelinated/drug effects , Nerve Fibers, Myelinated/physiology , Nerve Fibers, Myelinated/radiation effects , Osteotomy, Le Fort/adverse effects , Osteotomy, Sagittal Split Ramus/adverse effects , Postoperative Complications/radiotherapy , Prospective Studies , Sensory Thresholds/physiology , Somatosensory Disorders/radiotherapy , Young Adult
4.
Biomed Mater Eng ; 24(6): 3629-36, 2014.
Article in English | MEDLINE | ID: mdl-25227077

ABSTRACT

Demyelination is part of the cascading secondary injury after the primary insult and contributes to the loss of function after spinal cord injury (SCI). Oligodendrocyte precursor cells (OPCs) are the main remyelinating cells in the central nervous system (CNS). We explored whether oscillating field stimulation (OFS) could efficiently promote OPC differentiation and improve remyelination after SCI. SD rats with SCI induced by the Allen method were randomly divided into two groups, the SCI+OFS group and SCI group. The former group received active stimulator units and the latter group received sham (inoperative) stimulator units. Additionally, rats that only received laminectomy were referred as the sham group. The electric field intensity was 600 µV/mm, and the polarity was alternated every 15 minutes. The results showed that the SCI+OFS rats had significantly less demyelination and better locomotor function recovery after 12-weeks treatment. The OFS treatment significantly increased the number of Gal C-positive OPCs after 2-weeks treatment. Furthermore, these rats had higher protein expression of oligodendroglial transcription factors Olig2 and NKx2.2. These findings suggest OFS can promote locomotor recovery and remyelination in SCI rats and this effect may be related to the improved differentiation of OPCs in the spinal cord.


Subject(s)
Nerve Fibers, Myelinated/pathology , Nerve Regeneration/radiation effects , Oligodendroglia/pathology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/therapy , Spinal Cord Stimulation/methods , Stem Cells/cytology , Animals , Cell Differentiation/radiation effects , Female , Homeobox Protein Nkx-2.2 , Nerve Fibers, Myelinated/radiation effects , Oscillometry/methods , Rats , Rats, Sprague-Dawley , Spinal Cord/pathology , Stem Cells/radiation effects , Treatment Outcome
5.
PLoS One ; 9(2): e88244, 2014.
Article in English | MEDLINE | ID: mdl-24505446

ABSTRACT

Since approximately two thirds of epileptic patients are non-eligible for surgery, local axonal fiber transections might be of particular interest for them. Micrometer to millimeter wide synchrotron-generated X-ray beamlets produced by spatial fractionation of the main beam could generate such fiber disruptions non-invasively. The aim of this work was to optimize irradiation parameters for the induction of fiber transections in the rat brain white matter by exposure to such beamlets. For this purpose, we irradiated cortex and external capsule of normal rats in the antero-posterior direction with a 4 mm×4 mm array of 25 to 1000 µm wide beamlets and entrance doses of 150 Gy to 500 Gy. Axonal fiber responses were assessed with diffusion tensor imaging and fiber tractography; myelin fibers were examined histopathologically. Our study suggests that high radiation doses (500 Gy) are required to interrupt axons and myelin sheaths. However, a radiation dose of 500 Gy delivered by wide minibeams (1000 µm) induced macroscopic brain damage, depicted by a massive loss of matter in fiber tractography maps. With the same radiation dose, the damage induced by thinner microbeams (50 to 100 µm) was limited to their paths. No macroscopic necrosis was observed in the irradiated target while overt transections of myelin were detected histopathologically. Diffusivity values were found to be significantly reduced. A radiation dose ≤ 500 Gy associated with a beamlet size of < 50 µm did not cause visible transections, neither on diffusion maps nor on sections stained for myelin. We conclude that a peak dose of 500 Gy combined with a microbeam width of 100 µm optimally induced axonal transections in the white matter of the brain.


Subject(s)
Axons/pathology , Brain/pathology , Diffusion Tensor Imaging/methods , Animals , Axons/radiation effects , Brain/radiation effects , Myelin Sheath/pathology , Myelin Sheath/radiation effects , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Radiation Dosage , Rats , Synchrotrons , X-Rays
6.
J Clin Oncol ; 31(27): 3378-88, 2013 Sep 20.
Article in English | MEDLINE | ID: mdl-23960182

ABSTRACT

PURPOSE: CNS-directed chemotherapy (CT) and cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia or lymphoma have various neurotoxic properties. This study aimed to assess their impact on the maturing brain 20 to 30 years after diagnosis, providing a much stronger perspective on long-term quality of life than previous studies. PATIENTS AND METHODS: Ninety-three patients treated between 1978 and 1990 at various intensities, with and without CRT, and 49 healthy controls were assessed with magnetic resonance diffusion tensor imaging (DTI) and neuropsychological tests. Differences in fractional anisotropy (FA)-a DTI measure describing white matter (WM) microstructure-were analyzed by using whole brain voxel-based analysis. RESULTS: CRT-treated survivors demonstrated significantly decreased FA compared with controls in frontal, parietal, and temporal WM tracts. Trends for lower FA were seen in the CT-treated survivors. Decreases in FA correlated well with neuropsychological dysfunction. In contrast to the CT group and controls, the CRT group showed a steep decline of FA with age at assessment. Younger age at cranial irradiation and higher dosage were associated with worse outcome of WM integrity. CONCLUSION: CRT-treated survivors show decreased WM integrity reflected by significantly decreased FA and associated neuropsychological dysfunction 25 years after treatment, although effects of CT alone seem mild. Accelerated aging of the brain and increased risk of early onset dementia are suspected after CRT, but not after CT.


Subject(s)
Brain/pathology , Lymphoma/pathology , Nerve Fibers, Myelinated/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Adolescent , Adult , Brain/drug effects , Brain/radiation effects , Case-Control Studies , Chemoradiotherapy/adverse effects , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Lymphoma/drug therapy , Lymphoma/radiotherapy , Male , Nerve Fibers, Myelinated/drug effects , Nerve Fibers, Myelinated/radiation effects , Neuropsychological Tests , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/radiotherapy , Survivors , Young Adult
7.
PLoS One ; 8(3): e57768, 2013.
Article in English | MEDLINE | ID: mdl-23469234

ABSTRACT

PURPOSE: There is little known about how brain white matter structures differ in their response to radiation, which may have implications for radiation-induced neurocognitive impairment. We used diffusion tensor imaging (DTI) to examine regional variation in white matter changes following chemoradiotherapy. METHODS: Fourteen patients receiving two or three weeks of whole-brain radiation therapy (RT) ± chemotherapy underwent DTI pre-RT, at end-RT, and one month post-RT. Three diffusion indices were measured: fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). We determined significant individual voxel changes of diffusion indices using tract-based spatial statistics, and mean changes of the indices within fourteen white matter structures of interest. RESULTS: Voxels of significant FA decreases and RD increases were seen in all structures (p<0.05), with the largest changes (20-50%) in the fornix, cingula, and corpus callosum. There were highly significant between-structure differences in pre-RT to end-RT mean FA changes (p<0.001). The inferior cingula had a mean FA decrease from pre-RT to end-RT significantly greater than 11 of the 13 other structures (p<0.00385). CONCLUSIONS: Brain white matter structures varied greatly in their response to chemoradiotherapy as measured by DTI changes. Changes in FA and RD related to white matter demyelination were prominent in the cingula and fornix, structures relevant to radiation-induced neurocognitive impairment. Future research should evaluate DTI as a predictive biomarker of brain chemoradiotherapy adverse effects.


Subject(s)
Brain Neoplasms/pathology , Corpus Callosum/pathology , Fornix, Brain/pathology , Gyrus Cinguli/pathology , Melanoma/pathology , Adult , Aged , Antineoplastic Agents/therapeutic use , Brain Neoplasms/therapy , Chemoradiotherapy , Cognition/drug effects , Cognition/radiation effects , Corpus Callosum/drug effects , Corpus Callosum/radiation effects , Demyelinating Diseases , Diffusion Tensor Imaging , Female , Fornix, Brain/drug effects , Fornix, Brain/radiation effects , Gamma Rays , Gyrus Cinguli/drug effects , Gyrus Cinguli/radiation effects , Humans , Male , Melanoma/therapy , Middle Aged , Nerve Fibers, Myelinated/drug effects , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Prospective Studies
8.
J Magn Reson Imaging ; 37(1): 101-8, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22972703

ABSTRACT

PURPOSE: To detect radiation-induced changes of temporal lobe normal-appearing white mater (NAWM) following radiation therapy (RT) for nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Seventy-five H(1)-MR spectroscopy and diffusion-tensor imaging (DTI) examinations were performed in 55 patients before and after receiving fractionated radiation therapy (total dose; 66-75GY). We divided the dataset into six groups, a pre-RT control group and five other groups based on time after completion of RT. N-acetylaspartic acid (NAA)/choline (Cho), NAA/creatine (Cr), Cho/Cr, mean diffusibility (MD), functional anisotropy (FA), radial diffusibility (λ(⊥)), and axial diffusibility (λ(||)) were calculated. RESULTS: NAA/Cho and NAA/Cr decreased and λ(⊥) increased significantly within 1 year after RT compared with pre-RT. After 1 year, NAA/Cho, NAA/Cr, and λ(⊥) were not significantly different from pre-RT. In all post-RT groups, FA decreased significantly. λ(||) decreased within 9 months after RT compared with pre-RT, but was not significantly different from pre-RT more than 9 months after RT. CONCLUSION: DTI and H(1)-MR spectroscopy can be used to detect early radiation-induced changes of temporal lobe NAWM following radiation therapy for NPC. Metabolic alterations and water diffusion characteristics of temporal lobe NAWM in patients with NPC after RT were dynamic and transient.


Subject(s)
Brain Neoplasms/pathology , Brain/pathology , Diffusion Tensor Imaging/methods , Magnetic Resonance Spectroscopy/methods , Nasopharyngeal Neoplasms/pathology , Radiation Injuries/diagnosis , Temporal Lobe/pathology , Adult , Aged , Anisotropy , Biomarkers/metabolism , Brain/radiation effects , Brain Neoplasms/radiotherapy , Carcinoma , Decision Making , Diffusion , Dose Fractionation, Radiation , Female , Humans , Male , Middle Aged , Models, Statistical , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/radiotherapy , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Radiation Injuries/pathology , Radiotherapy/adverse effects , Temporal Lobe/radiation effects
9.
Nat Rev Neurol ; 8(10): 578-88, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22964509

ABSTRACT

The brain is highly vulnerable to neurotoxic agents during the prime learning period of a child's life. Paediatric patients with brain tumours who are treated with cranial radiation therapy (CRT) often go on to develop neurocognitive deficits, which are reflected in poor academic achievement and impaired memory, attention and processing speed. The extent of these delayed effects varies with radiation dose, brain volume irradiated, and age at treatment, and might also be influenced by genetic factors and individual susceptibility. CRT-induced impairment involves axonal damage and disruption of white matter growth, and can affect brain structures implicated in memory function and neurogenesis, such as the hippocampus. In this article, we review the underlying mechanisms and clinical consequences of CRT-induced neurocognitive damage in survivors of paediatric brain tumours. We discuss the recent application of neuroimaging technologies to identify white matter injury following CRT, and highlight new radiation techniques, pharmacological and neurological interventions, as well as rehabilitation programmes that have potential to minimize neurocognitive impairment following CRT.


Subject(s)
Brain Neoplasms/physiopathology , Brain Neoplasms/radiotherapy , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Cognition/radiation effects , Cranial Irradiation/adverse effects , Animals , Child , Cognition/physiology , Cognition Disorders/prevention & control , Humans , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Neuronal Plasticity/physiology , Neuronal Plasticity/radiation effects
10.
PLoS One ; 7(4): e35817, 2012.
Article in English | MEDLINE | ID: mdl-22558230

ABSTRACT

Brief high-power laser pulses applied onto the hairy skin of the distal end of a limb generate a double sensation related to the activation of Aδ- and C-fibres, referred to as first and second pain. However, neurophysiological and behavioural responses related to the activation of C-fibres can be studied reliably only if the concomitant activation of Aδ-fibres is avoided. Here, using a novel CO(2) laser stimulator able to deliver constant-temperature heat pulses through a feedback regulation of laser power by an online measurement of skin temperature at target site, combined with an adaptive staircase algorithm using reaction-time to distinguish between responses triggered by Aδ- and C-fibre input, we show that it is possible to estimate robustly and independently the thermal detection thresholds of Aδ-fibres (46.9±1.7°C) and C-fibres (39.8±1.7°C). Furthermore, we show that both thresholds are dependent on the skin temperature preceding and/or surrounding the test stimulus, indicating that the Aδ- and C-fibre afferents triggering the behavioural responses to brief laser pulses behave, at least partially, as detectors of a change in skin temperature rather than as pure level detectors. Most importantly, our results show that the difference in threshold between Aδ- and C-fibre afferents activated by brief laser pulses can be exploited to activate C-fibres selectively and reliably, provided that the rise in skin temperature generated by the laser stimulator is well-controlled. Our approach could constitute a tool to explore, in humans, the physiological and pathophysiological mechanisms involved in processing C- and Aδ-fibre input, respectively.


Subject(s)
Nerve Fibers, Myelinated/physiology , Nerve Fibers, Unmyelinated/physiology , Nociceptors/physiology , Pain Threshold/physiology , Skin/radiation effects , Adult , Evoked Potentials, Somatosensory/physiology , Evoked Potentials, Somatosensory/radiation effects , Female , Hot Temperature , Humans , Lasers, Gas , Male , Nerve Fibers, Myelinated/radiation effects , Nerve Fibers, Unmyelinated/radiation effects , Nociceptors/radiation effects , Pain Threshold/radiation effects , Reaction Time/physiology , Reaction Time/radiation effects , Skin Temperature/radiation effects
11.
Brain Res ; 1351: 23-31, 2010 Sep 10.
Article in English | MEDLINE | ID: mdl-20599817

ABSTRACT

Greater than 50% of adults and approximately 100% of children who survive >6 months after fractionated partial or whole-brain radiotherapy develop cognitive impairments. Noninvasive methods are needed for detecting and tracking the radiation-induced brain injury associated with these impairments. Using magnetic resonance imaging, we sought to detect structural changes associated with brain injury in our rodent model of fractionated whole-brain irradiation (fWBI) induced cognitive impairment and to compare those changes with alterations that occur during the aging process. Middle aged rats were given a clinically relevant dose of fWBI (40 Gy: two 5 Gy fractions/week for 4 weeks) and scanned approximately 1 year post-irradiation to obtain whole-brain T2 and diffusion tensor images (DTI); control groups of sham-irradiated age-matched and young rats were also scanned. No gross structural changes were evident in the T2 structural images, and no detectable fWBI-induced DTI changes in fractional anisotropy (FA) were found in heavily myelinated white matter (corpus callosum, cingulum, and deep cortical white matter). However, significant fWBI-induced variability in FA distribution was present in the superficial parietal cortex due to an fWBI-induced decline in FA in the more anterior slices through parietal cortex. Young rats had significantly lower FA values relative to both groups of older rats, but only within the corpus callosum. These findings suggest that targets of the fWBI-induced change in this model may be the less myelinated or unmyelinated axons, extracellular matrix, or synaptic fields rather than heavily myelinated tracts.


Subject(s)
Aging/metabolism , Aging/radiation effects , Brain/metabolism , Brain/radiation effects , Diffusion Tensor Imaging , Dose Fractionation, Radiation , Age Factors , Animals , Anisotropy , Diffusion Tensor Imaging/methods , Male , Nerve Fibers, Myelinated/metabolism , Nerve Fibers, Myelinated/radiation effects , Rats , Rats, Inbred BN , Rats, Inbred F344
12.
J Neurol Sci ; 285(1-2): 178-84, 2009 Oct 15.
Article in English | MEDLINE | ID: mdl-19625028

ABSTRACT

Radiation therapy is used widely to treat primary and metastatic brain tumors, but also can lead to delayed neurological complications. Since maintenance of myelin integrity is important for cognitive function, the present study used a rat model that demonstrates spatial learning and memory impairment 12 months following fractionated whole-brain irradiation (WBI) at middle age to investigate WBI-induced myelin changes. In this model, 12-month Fischer 344 x Brown Norway rats received 9 fractions of 5 Gy delivered over 4.5 weeks (WBI rats); Sham-IR rats received anesthesia only. Twelve months later, the brains were collected and measures of white matter integrity were quantified. Qualitative observation did not reveal white matter necrosis one year post-WBI. In addition, the size of major forebrain commissures, the number of oligodendrocytes, the size and number of myelinated axons, and the thickness of myelin sheaths did not differ between the two groups. In summary, both the gross morphology and the structural integrity of myelin were preserved one year following fractionated WBI in a rodent model of radiation-induced cognitive impairment. Imaging studies with advanced techniques including diffusion tensor imaging may be required to elucidate the neurobiological changes associated with the cognitive impairment in this model.


Subject(s)
Brain/pathology , Brain/radiation effects , Cognition Disorders/pathology , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Radiation Injuries, Experimental/pathology , Animals , Brain/ultrastructure , Cell Count , Cell Size , Cognition Disorders/etiology , Disease Models, Animal , Learning Disabilities/etiology , Learning Disabilities/pathology , Male , Memory Disorders/etiology , Memory Disorders/pathology , Myelin Sheath/pathology , Myelin Sheath/radiation effects , Myelin Sheath/ultrastructure , Necrosis/pathology , Nerve Fibers, Myelinated/ultrastructure , Oligodendroglia/pathology , Oligodendroglia/radiation effects , Oligodendroglia/ultrastructure , Organ Size , Random Allocation , Rats , Rats, Inbred F344 , Space Perception/radiation effects , Time Factors
13.
Surg Neurol ; 72(5): 496-500; discussion 501, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19329170

ABSTRACT

BACKGROUND: PRF treatment has recently been described as minimally neurodestructive alternative to radiofrequency heat lesions. Patients with some pain syndromes in whom the pain could not be controlled by alternative techniques may be treated using PRF. In the present study, our main goal was to evaluate and compare the ultrastructure of peripheral nerve tissue that was heated by PRF, CRF with 42 degrees C, and CRF with 70 degrees C. METHODS: Forty-five male rats were divided into 5 groups. In PRF group and CRF with 42 degrees C group, the sciatic nerve was heated at a temperature of 42 degrees C for 120 seconds. As a positive control, some rat sciatic nerves were treated with CRF lesions at 70 degrees C. The rats were kept alive for 21 days and then killed. Tissue was evaluated with transmission electron microscope, and grading was done to the groups. RESULTS: The unmyelinated nerve fibers were ultrastructurally normal in all groups. The results of myelinated axons indicated that PRF group had better grades, and CRF with 70 degrees C group had the worst grade. Especially, comparison of the group of PRF and CRF with 42 degrees C revealed significant difference. In PRF group, none of the myelinated axons showed severe degeneration findings, and most of the damaged myelinated axons showed only separation in myelin configuration. CONCLUSIONS: PRF treatment may cause separation in myelinated axons. However, it seems that all changes were reversible. The present study supports the hypothesis that pulsed RF treatment does not rely on thermal injury of neurologic tissue to achieve its effect.


Subject(s)
Catheter Ablation/methods , Pain, Intractable/surgery , Peripheral Nervous System Diseases/surgery , Sciatic Nerve/radiation effects , Sciatic Nerve/surgery , Sciatic Neuropathy/etiology , Animals , Disease Models, Animal , Hot Temperature/adverse effects , Male , Microscopy, Electron, Transmission , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Nerve Fibers, Unmyelinated/pathology , Nerve Fibers, Unmyelinated/radiation effects , Nociceptors/pathology , Nociceptors/radiation effects , Pain, Intractable/physiopathology , Peripheral Nervous System Diseases/physiopathology , Rats , Rats, Wistar , Sciatic Nerve/pathology , Sciatic Neuropathy/pathology , Sciatic Neuropathy/physiopathology , Wallerian Degeneration/etiology , Wallerian Degeneration/pathology , Wallerian Degeneration/physiopathology
14.
Eur Spine J ; 18(4): 473-8, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19172311

ABSTRACT

Since the dorsal root ganglia represent the first structure of pain modulation, they are the target of the newest therapies of neuropathic pain. Between these, pulsed radiofrequency (PRF) has been described among the promising non-invasive methods. Although the results encourage the clinical use of this procedure, their mechanism of action is still unclear. Aim of our study was to analyze acute effects of PRF on the rat lumbar ganglion and on nervous fibres running inside it. Clinical works describe PRF treatment as a technique without any visible neurological deficit. The few disposable histological works are contractictory: some describe no signs of cellular damage and some demonstrate visible intracellular modifications. A total of 20 male Wistar rats were deeply anesthesized. Ten were positioned in a stereotactic system, and exposed to PRF at 2 Hz for 30 s after exposition of paravertebral muscles and positioning of a stimulation needle on left L4 ganglion. The other ten were used as controls. After 1 h, the left dorsal root ganglions L3, L4, L5 of the 20 animals were explanted, fixed in 2.5% Karnowsky solution and prepared for light and transmission electron microscopy. At light microscopy no differences between treated and control animals were observed; at transmission electron microscopy, instead, it was possible to observe that T gangliar cells contained an abnormal abundant smooth reticulum with enlarged cisternae and numerous vacuoles; myelinated axons presented pathological features and their myelin coverage was not adherent. Instead, unmyelinated axons appeared normal in shape and dimension and the Schwann cells surrounding it had intact plasmamembrane. Our results, obtained at acute stage, reveal that the PRF procedure should destroy the myelin envelope of nervous fibres. Further future studies, at chronic stage, should give other information on the prognosis of the myelinic damage.


Subject(s)
Catheter Ablation/adverse effects , Ganglia, Spinal/radiation effects , Nerve Degeneration/etiology , Nociceptors/radiation effects , Peripheral Nervous System Diseases/therapy , Sensory Receptor Cells/radiation effects , Acute Disease , Animals , Catheter Ablation/methods , Disease Models, Animal , Endoplasmic Reticulum, Smooth/pathology , Endoplasmic Reticulum, Smooth/radiation effects , Ganglia, Spinal/pathology , Ganglia, Spinal/physiopathology , Male , Microscopy, Electron, Transmission , Nerve Degeneration/pathology , Nerve Degeneration/physiopathology , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Neuralgia/pathology , Neuralgia/physiopathology , Neuralgia/therapy , Nociceptors/pathology , Peripheral Nervous System Diseases/pathology , Peripheral Nervous System Diseases/physiopathology , Rats , Rats, Wistar , Sensory Receptor Cells/pathology , Wallerian Degeneration/etiology , Wallerian Degeneration/pathology , Wallerian Degeneration/physiopathology
15.
Neurosurgery ; 63(6): 1064-9; discussion 1069-70, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19008768

ABSTRACT

OBJECTIVE: Perinidal high-signal-intensity changes on T2-weighted magnetic resonance imaging can be seen surrounding radiosurgically treated brain arteriovenous malformations (AVM). Occasionally, these signal intensity changes develop far beyond the irradiated volume. A retrospective analysis of both the pre- and postradiosurgery magnetic resonance imaging and angiographic studies was performed to analyze the cause of these extensive perinidal white matter changes. METHODS: The pre- and postradiosurgical magnetic resonance imaging and angiographic studies of 30 patients with T2 high-signal-intensity changes surrounding a brain AVM were analyzed retrospectively. Patients were divided into 2 groups on the basis of the extension of the signal intensity changes within or beyond the 10-Gy isodose area. The angiographic analysis was focused on the venous drainage pattern (deep versus superficial), venous stenosis, and the number of draining veins before and after radiosurgery. In addition, the obliteration rate was determined for the 2 subgroups. RESULTS: Fourteen patients (47%) showed high-signal-intensity changes far beyond the 10-Gy isodose area. A single draining vein was more often present in these patients with extensive T2 hyperintensity signal changes than in the other group. Obliteration was achieved in 12 (88%) of 14 patients with extensive signal intensity changes, as opposed to 8 (50%) of 16 patients in the other group. CONCLUSION: High-signal-intensity changes after radiosurgery for brain AVMs, far beyond the 10-Gy isodose area on T2-weighted images, are especially seen in brain AVMs draining through a single vein. The higher occlusion rate of brain AVMs under these circumstances is well appreciated.


Subject(s)
Brain Injuries/etiology , Brain Injuries/pathology , Intracranial Arteriovenous Malformations/surgery , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Radiation Injuries/etiology , Radiation Injuries/pathology , Radiosurgery/adverse effects , Adult , Female , Humans , Male , Retrospective Studies , Treatment Outcome
16.
J Child Neurol ; 23(10): 1160-71, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18952582

ABSTRACT

Neurocognitive late effects are common sequelae of cancer in children, especially in those who have undergone treatment for brain tumors or in those receiving prophylactic cranial radiation therapy to treat leukemia. Neurocognitive morbidity in attention, executive functioning, processing speed, working memory, and memory frequently occurs and contributes to declines in intellectual and academic abilities. Oncologists are faced with the challenge of using the most effective, often the most intense, therapy to achieve the primary goal of medical success, balanced with the desire to prevent adverse late effects. Not all children with similar diagnoses and treatment have identical neurocognitive outcomes; some do very poorly and some do well. Attention now turns to the reliable prediction of risk for poor outcomes and then, using risk-adapted therapy, to preserve neurocognitive function. Prevention of late effects through rehabilitative strategies, continuation of school, and pharmacotherapy will be explored.


Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Brain/drug effects , Brain/radiation effects , Cognition Disorders/prevention & control , Drug-Related Side Effects and Adverse Reactions , Radiotherapy/adverse effects , Age Factors , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Brain/physiopathology , Brain Neoplasms/mortality , Child , Cognition Disorders/chemically induced , Cognition Disorders/physiopathology , Drug Therapy/methods , Drug Therapy/trends , Humans , Iatrogenic Disease/prevention & control , Nerve Fibers, Myelinated/drug effects , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Radiotherapy/methods , Radiotherapy/trends , Time
17.
J Neurophysiol ; 100(5): 2794-806, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18784270

ABSTRACT

Previous studies have demonstrated that locally administered cannabinoids attenuate allodynia and hyperalgesia through activation of peripheral cannabinoid receptors (CB(1) and CB(2)). However, it is currently unknown if cannabinoids alter the response properties of nociceptors. In the present study, correlative behavioral and in vivo electrophysiological studies were conducted to determine if peripheral administration of the cannabinoid receptor agonists arachidonyl-2'-chloroethylamide (ACEA) or (R)-(+)-methanandamide (methAEA) could attenuate mechanical allodynia and hyperalgesia, and decrease mechanically evoked responses of Adelta nociceptors. Twenty-four hours after intraplantar injection of complete Freund's adjuvant (CFA), rats exhibited allodynia (decrease in paw withdrawal threshold) and hyperalgesia (increase in paw withdrawal frequency), which were attenuated by both ACEA and methAEA. The antinociceptive effects of these cannabinoids were blocked by co-administration with the CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) but not with the CB(2) receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-y l](4-methoxyphenyl)methanone (AM630). ACEA and methAEA did not produce antinociception under control, non-inflamed conditions 24 h after intraplantar injection of saline. In parallel studies, recordings were made from cutaneous Adelta nociceptors from inflamed or control, non-inflamed skin. Both ACEA and methAEA decreased responses evoked by mechanical stimulation of Adelta nociceptors from inflamed skin but not from non-inflamed skin, and this decrease was blocked by administration of the CB(1) receptor antagonist AM251. These results suggest that attenuation of mechanically evoked responses of Adelta nociceptors contributes to the behavioral antinociception produced by activation of peripheral CB(1) receptors during inflammation.


Subject(s)
Cannabinoids/metabolism , Inflammation/pathology , Nerve Fibers, Myelinated/physiology , Nociceptors/metabolism , Skin/innervation , Action Potentials/drug effects , Action Potentials/physiology , Action Potentials/radiation effects , Analysis of Variance , Animals , Arachidonic Acids/pharmacology , Cannabinoids/antagonists & inhibitors , Dose-Response Relationship, Drug , Drug Interactions , Freund's Adjuvant , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/physiopathology , Male , Nerve Fibers, Myelinated/drug effects , Nerve Fibers, Myelinated/radiation effects , Neural Conduction/drug effects , Neural Conduction/physiology , Pain Measurement/methods , Pain Threshold/drug effects , Piperidines/pharmacology , Pyrazoles/pharmacology , Rats , Rats, Sprague-Dawley , Reaction Time/drug effects , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Receptor, Cannabinoid, CB2/antagonists & inhibitors
18.
Radiat Med ; 26(3): 140-50, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18683569

ABSTRACT

PURPOSE: The aim of this study was to ascertain whether diffusion tensor imaging (DTI) metrics fractional anisotropy (FA), mean diffusivity (MD), linear case (CL), planar case (CP), spherical case (CS)-can characterize a threshold dose and temporal evolution of changes in normal-appearing white matter (NAWM) of adults with low-grade gliomas (LGGs) treated with radiation therapy (RT). METHODS AND MATERIALS: Conventional and DTI imaging were performed before RT in 5 patients and subsequently, on average, at 3 months (n = 5), 8 months (n = 3), and 14 months (n = 5) following RT for a total of 18 examinations. Isodose distribution at 5-Gy intervals were visualized in all the slices of fluid attenuated inversion recovery (FLAIR) and the corresponding DTI images without diffusion sensitization (b0DTI). The latter were exported for relative quantitative analysis. RESULTS: Compared to pre-RT values, FA and CL decreased, whereas CS increased at 3 and 8 months and recovered partially at 14 months for the dose bins >55 Gy and 50-55 Gy. For the 45 50 Gy bin, the FA and CL decreased with an increase in CS at 3 months; no further change was seen at 8 or 14 months. For the >55 Gy and 50-55 Gy bins, CP decreased and MD increased at 3 months and returned to baseline at 8 months following RT. CONCLUSION: Radiation-induced changes in NAWM can be detected at 3 months after RT, with changes in FA, CL, and CS (but not CP or MD) values seen at a threshold dose of 45-50 Gy. A partial recovery was evident by 14 months to regions that received doses of 50-55 Gy and >55 Gy, thus providing an objective measure of radiation effect on NAWM.


Subject(s)
Brain Neoplasms/radiotherapy , Diffusion Magnetic Resonance Imaging , Glioma/radiotherapy , Nerve Fibers, Myelinated/radiation effects , Radiation Injuries/diagnosis , Adult , Analysis of Variance , Anisotropy , Brain Neoplasms/pathology , Dose-Response Relationship, Radiation , Female , Glioma/pathology , Humans , Image Interpretation, Computer-Assisted , Male , Radiotherapy Dosage
19.
Clin Neurophysiol ; 119(8): 1905-1908, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18556243

ABSTRACT

OBJECTIVE: Although laser stimuli activate both Adelta- and C-fibres, the corresponding laser evoked potentials (LEPs) remain restricted to the Adelta-fibre input. Previous studies found C-LEPs after limb stimulation only in subjects with block or clinical impairment of Adelta-fibres. In this study, we aimed at verifying whether in the trigeminal territory the impairment of Adelta-fibres unmasks the C-LEP. METHODS: By collecting retrospectively LEPs recorded in 370 patients, we analyzed the results from 150 trigeminal divisions with absent Adelta-LEPs. RESULTS: We found signals that were consistent with the C-fibre input in three patients only. In most patients with absent Adelta-LEPs, however, laser stimuli still elicited the Adelta-conveyed pinprick sensation. CONCLUSIONS: The preserved pinprick sensation suggests that the Adelta-fibre volley, though weakened, reached the cortex. The C-LEP absence may be explained according to the first come first served hypothesis: the evoked potential related to an afferent volley reaching the cortex shortly after a preceding input (i.e. a C-fibre volley coming after an Adelta-fibre) will be suppressed. SIGNIFICANCE: In clinical studies using the standard laser pulses to evoke the Adelta-LEPs, the finding of absent signals does not indicate a concomitant impairment of C-fibres.


Subject(s)
Evoked Potentials/radiation effects , Lasers , Nerve Fibers, Myelinated/radiation effects , Nerve Fibers, Myelinated/ultrastructure , Nerve Fibers, Unmyelinated/radiation effects , Trigeminal Nerve Diseases/pathology , Trigeminal Nerve Diseases/physiopathology , Adult , Aged , Aged, 80 and over , Evoked Potentials/physiology , Female , Humans , Male , Microscopy, Electron, Transmission/methods , Middle Aged , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/physiology , Nerve Fibers, Unmyelinated/physiology , Retrospective Studies
20.
AJNR Am J Neuroradiol ; 29(2): 379-83, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17974610

ABSTRACT

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) will show abnormal fractional anisotropy (FA) in the normal-appearing brain after prophylactic cranial irradiation (PCI). These abnormalities will be more accentuated in patients with underlying vascular risk factors. MATERIALS AND METHODS: A prospective study by use of DTI and conventional T2-weighted MR images was performed with a 1.5T unit with 16 patients with small cell lung cancer and undergoing PCI. All of the T2-weighted images were evaluated with respect to abnormalities in signal intensity of white matter as markers of radiation damage. Measurements of FA were performed before, at the end of, and 6 weeks after radiation therapy. On the FA maps, the bifrontal white matter, the corona radiata, the cerebellum, and the brain stem were evaluated. FA values were compared with respect to age, demographic, and vascular risk factors. Statistical analyses (Friedman test, Wilcoxon test, and Mann-Whitney U test) were performed. RESULTS: Fractional anisotropy decreased significantly in supratentorial and infratentorial normal-appearing white matter from the beginning to the end of PCI (P < .01). A further decline in FA occurred 6 weeks after irradiation (P < .05). A stronger reduction in FA was observed in patients with more than 1 vascular risk factor. There was an age-related reduction of white matter FA. Patients 65 years and older showed a trend toward a stronger reduction in FA. CONCLUSION: During the acute phase, after PCI, patients with many vascular risk factors showed stronger damage in the white matter compared with patients with only 1 risk factor.


Subject(s)
Carcinoma, Small Cell/prevention & control , Carcinoma, Small Cell/radiotherapy , Diffusion Magnetic Resonance Imaging/methods , Lung Neoplasms/radiotherapy , Nerve Fibers, Myelinated/pathology , Nerve Fibers, Myelinated/radiation effects , Radiation Injuries/etiology , Radiation Injuries/pathology , Aged , Dose Fractionation, Radiation , Female , Humans , Lung Neoplasms/prevention & control , Magnetic Resonance Imaging/methods , Male , Middle Aged , Pilot Projects , Treatment Outcome
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