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1.
J Gene Med ; 24(3): e3402, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34897885

RESUMO

BACKGROUND: Despite the increasing availability of effective drugs, around one-third of patients with epilepsy are still resistant to pharmacotherapy. Gene therapy has been suggested as a plausible approach to achieve seizure control, in particular for patients with focal epilepsy. Because seizures develop across wide spans of the brain in many forms of epilepsy, global delivery of the vectors is necessary to tackle such generalized seizures. Neuroligin 2 (NL2) is a postsynaptic cell adhesion molecule that induces or strengthens inhibitory synaptic function by specifically combining with neurexin 1. METHODS: In the present study, we applied an adeno-associated virus (AAV) type 9 vector expressing NL2 to modulate neuronal excitability in broad areas of the brain in epileptic (EL) mice, a model of polygene epilepsy. We administered the AAV vector expressing Flag-tagged NL2 under the synapsin I promoter (AAV-NL2) via cardiac injection 6 weeks after birth. RESULTS: Significant reductions in the duration, strength and frequency of seizure were observed during a 14-week observation period in NL2-treated EL mice compared to untreated or AAV-green fluorescent protein-treated EL mice. No behavioral abnormality was observed in NL2-treated EL mice in an open-field test. Immunohistochemical examination at 14 weeks after AAV-NL2 injection revealed the expression of exogenous NL2 in broad areas of the brain, including the hippocampus and, in these areas, NL2 co-localized with postsynaptic inhibitory molecule gephyrin. CONCLUSIONS: Global brain delivery of NL2 by systemic administration of AAV vector may provide a non-invasive therapeutic approach for generalized epilepsy.


Assuntos
Epilepsia , Sinapses , Animais , Encéfalo , Moléculas de Adesão Celular Neuronais , Epilepsia/genética , Epilepsia/metabolismo , Epilepsia/terapia , Humanos , Camundongos , Proteínas do Tecido Nervoso , Convulsões/genética , Convulsões/metabolismo , Convulsões/terapia , Sinapses/metabolismo
2.
Mol Ther Methods Clin Dev ; 13: 180-186, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-30788386

RESUMO

Gene therapy has been employed as a therapeutic approach for intractable focal epilepsies. Considering the potential of focal GABAergic neuromodulation in regulating epileptogenesis, the GABA-producing enzyme, γ-aminobutyric acid decarboxylase 67 (GAD67), is highly suitable for epilepsy therapy. The EL/Suz (EL) mouse is a model of multifactorial temporal lobe epilepsy. In the present study, we examined focal gene transduction in epileptic EL mice using recombinant adeno-associated virus serotype 8 (rAAV8) expressing human GAD67 to enhance GABA-mediated neural inhibition. Eight-week-old mice were bilaterally injected with rAAV8-GFP or rAAV8-GAD67 in the hippocampal CA3 region. After four weeks, the GAD67-transduced EL mice, but not the rAAV-GFP-treated EL mice, exhibited a significant reduction in seizure generation. The GAD67-mediated depression became stable after 14 weeks. The excitability of the CA3 region was markedly reduced in the GAD67-transduced EL mice, consistent with the results of the Ca2+ imaging using hippocampal slices. In addition, downregulation of c-Fos expression was observed in GAD67-transduced hippocampi. Our findings showed that rAAV8-GAD67 induced significant changes in the GABAergic system in the EL hippocampus. Thus, rAAV8-mediated GAD67 gene transfer is a promising therapeutic strategy for the treatment of epilepsies.

3.
World Neurosurg ; 92: 171-178, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27178237

RESUMO

OBJECTIVE: Hemifacial spasm occurs when a blood vessel compresses against an area near the root exit zone of the facial nerve. Developments in diagnostic neuroimaging have allowed three-dimensional (3D) observation of artery and nerve locations, an effective aid for treatment selection. However, an accurate interpretation of the 3D data remains challenging because imaging representations of complex small vessels are drowned out by noise. We used a noise elimination method to analyze artery and nerve locations and to determine their 3D relationship. METHODS: Fifteen patients treated for hemifacial spasm were included. Images fused from 3 modalities of magnetic resonance imaging, 3D computed tomography, and angiography were used as source images. Using the images, models of the nerve and candidate vessels were created and shown in 3D to observe how the arteries were compressing the nerve and to identify the portions of the offending vessels that were closest to the nerve. These preoperative results were then compared with operative field observations during surgery. 3D models of the unaffected side were created and evaluated as controls. RESULTS: We confirmed that these models were accurate reconstructions of the source images as the tubular nerve and artery cross-sections showed good alignment onto magnetic resonance imaging axial slice images. The preoperative diagnoses of the compression sites and offending arteries all matched intraoperative findings. CONCLUSIONS: An accurate identification of the offending arteries and compression sites was possible, and this method is anticipated to offer effective means of preoperative simulation.


Assuntos
Espasmo Hemifacial/diagnóstico por imagem , Espasmo Hemifacial/cirurgia , Imageamento Tridimensional , Cirurgia de Descompressão Microvascular/métodos , Cuidados Pré-Operatórios , Adulto , Idoso , Idoso de 80 Anos ou mais , Nervo Facial/diagnóstico por imagem , Nervo Facial/cirurgia , Feminino , Humanos , Imageamento Tridimensional/métodos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Síndromes de Compressão Nervosa/etiologia , Resultado do Tratamento
4.
NMC Case Rep J ; 3(3): 67-70, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28664001

RESUMO

A 67-year-old man presented with consciousness disturbance and right hemiparesis. Computed tomography (CT) scan showed an intracerebral hematoma with two enhanced vascular lesions. Digital subtraction angiography revealed the dural arteriovenous fistula (dAVF) in the falx cerebri which was supplied by both bilateral middle meningeal arteries and left pericallosal artery and drained into both the superior sagittal sinus and the vein of Galen via the posterior callosal vein accompanied by two venous pouches. The dAVF was obliterated by a combination of the endovascular and the direct surgeries. A dAVF in a falx cerebri is very rare and only five cases were reported. Clinical characteristics of the dAVFs are uncertain. Before deciding the strategy of treatment, it is important to consider the pathological condition including embryology of the falx, the falcine sinus, and the falcine venous plexus.

5.
Neurophotonics ; 2(2): 025003, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26158007

RESUMO

Noninvasive localization of an epileptogenic zone is a fundamental step for presurgical evaluation of epileptic patients. Here, we applied long-term simultaneous functional near-infrared spectroscopy (fNIRS)/electroencephalogram (EEG) monitoring for focus diagnosis in patients with mesial temporal lobe epilepsy (MTLE). Six MTLE patients underwent long-term (8-16 h per day for 4 days) fNIRS/EEG monitoring for the occurrence of spontaneous seizures. Four spontaneous seizures were successfully recorded out of the six patients. To determine oxy-Hb amplitude, the period-average values of oxy-Hb across 20 s from the EEG- or clinically defined epileptic onset were calculated for both hemispheres from the simultaneously recorded fNIRS data. The average oxy-Hb values for the temporal lobe at the earlier EEG- or clinically defined epileptic onsets were greater for the epileptic side than for the contralateral side after EEG activity suppression, spike train, and clinical seizure in all four cases. The true laterality was determined based on the relief of seizures by selective amygdalo-hippocampectomy. Thus, oxy-Hb amplitude could be a reliable measure for determining the epileptic focus side. Long-term simultaneous fNIRS/EEG measurement serves as an effective tool for recording spontaneous seizures. Cerebral hemodynamic measurement by fNIRS would serve as a valuable supplementary noninvasive measurement method for presurgical evaluation of MTLE.

6.
Neuroimage ; 91: 138-45, 2014 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-24418508

RESUMO

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains.


Assuntos
Mapeamento Encefálico/métodos , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Cavidade Nasal/anatomia & histologia , Neuroimagem/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Algoritmos , Animais , Córtex Cerebral/fisiologia , Interpretação Estatística de Dados , Estimulação Elétrica , Eletromiografia , Potenciais Somatossensoriais Evocados/fisiologia , Hemoglobinas/metabolismo , Masculino , Cavidade Nasal/fisiologia , Oxiemoglobinas/metabolismo , Córtex Somatossensorial/fisiologia , Suínos
7.
Brain Lang ; 126(2): 208-16, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23800710

RESUMO

In Japan, verbal fluency tasks are commonly utilized as a standard paradigm for neuropsychological testing of cognitive and linguistic abilities. The Japanese "letter fluency task" is a mora/letter fluency task based on the phonological and orthographical characteristics of the Japanese language. Whether there are similar activation patterns across languages or a Japanese-specific mora/letter fluency pattern is not certain. We investigated the neural correlates of overt mora/letter and category fluency tasks in healthy Japanese. The category fluency task activated the bilateral fronto-temporal language-related regions with left-superior lateralization, while the mora/letter fluency task led to wider activation including the inferior parietal regions (left and right supramarginal gyrus). Specific bilateral supramarginal activation during the mora/letter fluency task in Japanese was distinct from that of similar letter fluency tasks in syllable-alphabet-based languages: this might be due to the requirement of additional phonological processing and working memory, or due to increased cognitive load in general.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiologia , Fala/fisiologia , Adulto , Povo Asiático , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Processamento de Sinais Assistido por Computador , Espectroscopia de Luz Próxima ao Infravermelho , Adulto Jovem
8.
J Neurosci Methods ; 212(1): 100-5, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23036661

RESUMO

There is an increasing need for a pig model for use in functional brain studies, but a system for determining precise stereotactic coordinates has yet to be developed. Thus, we devised a frameless navigation system for stereotactic positioning, and measured coordinates for the rostral region and the primary somatosensory cortex in the pig brain. Raw coordinates for somatic evoked potential recordings were obtained by passive optical tracking. The location was registered to a computed tomographic image in reference to four stable skull landmarks: the upper margin of each auditory meatus, the external occipital protuberance, and the point where the interfrontal suture crosses a line drawn between the two supraorbital foramina ("IF" point). The cortical position with the greatest response in evoked potential was mapped -51.0 ± 4.67 mm rostro-caudally, 9.1 ± 1.19 mm medio-laterally, and -8.8 ± 0.48 mm dorso-ventrally (means ± SD; n=3) to the IF point. These results show that frameless registration is useful for coordinate-based evoked-potential mapping of the rostral region of the Mexican hairless pig.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Potenciais Evocados/fisiologia , Neuronavegação/métodos , Animais , Encéfalo/anatomia & histologia , Estimulação Elétrica/instrumentação , Estimulação Elétrica/métodos , Eletroencefalografia , Feminino , Imageamento Tridimensional , Masculino , Neuronavegação/instrumentação , Técnicas Estereotáxicas , Suínos , Tomógrafos Computadorizados
9.
Brain Lang ; 121(3): 185-93, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22429907

RESUMO

Confrontation naming tasks assess cognitive processes involved in the main stage of word production. However, in fMRI, the occurrence of movement artifacts necessitates the use of covert paradigms, which has limited clinical applications. Thus, we explored the feasibility of adopting multichannel functional near-infrared spectroscopy (fNIRS) to assess language function during covert and overt naming tasks. Thirty right-handed, healthy adult volunteers underwent both naming tasks and cortical hemodynamics measurement using fNIRS. The overt naming task recruited the classical left-hemisphere language areas (left inferior frontal, superior and middle temporal, precentral, and postcentral gyri) exemplified by an increase in the oxy-Hb signal. Activations were bilateral in the middle and superior temporal gyri. However, the covert naming task recruited activation only in the left-middle temporal gyrus. The activation patterns reflected a major part of the functional network for overt word production, suggesting the clinical importance of fNIRS in the diagnosis of aphasic patients.


Assuntos
Mapeamento Encefálico/métodos , Córtex Cerebral/fisiologia , Fala/fisiologia , Adulto , Córtex Cerebral/irrigação sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Processamento de Sinais Assistido por Computador , Espectroscopia de Luz Próxima ao Infravermelho , Adulto Jovem
10.
Life Sci ; 77(23): 2867-78, 2005 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-15961120

RESUMO

Pretreatment with a low dose of 3-nitropropionic acid (3-NPA) has been shown to induce ischemic tolerance in the gerbil hippocampus. It is well known that sublethal (2-min) ischemia also induces ischemic tolerance. To investigate the acquisition of ischemic tolerance with 3-NPA, we examined the protein expression after 3-NPA treatment in comparison with sublethal ischemia. Immunohistochemical studies revealed intense expression of Bcl-2 and Bcl-xL in the hippocampal CA1 area after 3-NPA treatment. Furthermore, the time course of the expression of Bcl-xL showed a similar pattern to the acquisition of ischemic tolerance by 3-NPA treatment. The induction of Bcl-xL occurred in the hippocampal CA1 area at 24 h after 3-NPA treatment, and significant induction was observed at 48 h. Western blot analysis of hippocampus harvested 48 h after the pretreatment, showed that the expression of Bcl-2 and Bcl-xL was significantly increased by either 3-NPA treatment or 2-min ischemia. However, PMCA1 and HSP70 protein expression increased only in the sublethal ischemia treated group. The difference between 3-NPA treated group and control group was not statistically significant. These results suggest that Bcl-2 and Bcl-xL are essential for acquisition of ischemic tolerance, while HSP70 and PMCA1 play important roles in the enhancement of ischemic tolerance.


Assuntos
Adaptação Fisiológica , Hipocampo/metabolismo , Ataque Isquêmico Transitório/metabolismo , Precondicionamento Isquêmico/métodos , Fármacos Neuroprotetores/farmacologia , Propionatos/farmacologia , Proteínas/metabolismo , Animais , Western Blotting , ATPases Transportadoras de Cálcio/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Modelos Animais de Doenças , Gerbillinae , Proteínas de Choque Térmico HSP70/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Técnicas Imunoenzimáticas , Masculino , Nitrocompostos , ATPases Transportadoras de Cálcio da Membrana Plasmática , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína bcl-X
11.
Neurosci Lett ; 364(2): 101-5, 2004 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-15196687

RESUMO

Developing animals are known to be resistant to cerebral ischemia. To investigate the mechanisms by which developing animals exhibit ischemic resistance, we examined the changes in intracellular calcium ([Ca2+]i) after oxygen-glucose deprivation (OGD) using hippocampal slices from gerbils. We found that increases of [Ca2+]i in hippocampal CA1 neurons is significantly less after OGD in developing gerbils than in adults. Western blot analysis of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors (AMPARs) showed that GluR2 expression, but not that of the other AMPARs is significantly higher in developing gerbils than in adults. Expression of the anti-apoptotic proteins such as HSP70, Bcl-XL, and plasma membrane Ca2+-ATPase type1 (PMCA1) are not higher in the developing gerbils than in adults. These results suggest that the higher expression of GluR2 is important for the smaller increases in [Ca2+]i and enhanced resistance to ischemia-induced neuronal damage in developing animals.


Assuntos
Envelhecimento/fisiologia , Isquemia Encefálica/metabolismo , Cálcio/metabolismo , Receptores de AMPA/biossíntese , Receptores de AMPA/genética , Regulação para Cima/fisiologia , Animais , Western Blotting , ATPases Transportadoras de Cálcio/biossíntese , ATPases Transportadoras de Cálcio/genética , Artéria Carótida Primitiva/fisiologia , Corantes Fluorescentes , Gerbillinae , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico HSP70/genética , Hipocampo/metabolismo , Técnicas In Vitro
12.
Neurosci Lett ; 362(3): 216-9, 2004 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-15158018

RESUMO

In normal gerbils, intracellular zinc ions ([Zn2+]i) and calcium ions ([Ca2+]i) accumulate in hippocampal CA1 neurons after global ischemia. We examined whether ischemic preconditioning modifies these changes in gerbil hippocampal slices. In normal slices, large increases in [Zn2+]i and [Ca2+]i were observed in the stratum radiatum of the CA1 area after oxygen-glucose deprivation. In preconditioned slices, there were significantly decreased peak levels of [Zn2+]i and [Ca2+]i in CA1. However, there were no differences in the peak levels of these ions in CA3 and dentate gyrus. These results suggest that modified [Zn2+]i and [Ca2+]i accumulation after an ischemic insult might be important for the mechanisms of ischemic tolerance induced by preconditioning.


Assuntos
Glucose/deficiência , Hipocampo/citologia , Hipóxia/metabolismo , Isquemia/metabolismo , Neurônios/metabolismo , Zinco/metabolismo , Animais , Cálcio/metabolismo , Diagnóstico por Imagem/métodos , Espaço Extracelular/metabolismo , Gerbillinae , Técnicas In Vitro , Precondicionamento Isquêmico , Masculino
13.
Neurol Med Chir (Tokyo) ; 42(7): 297-300, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12160309

RESUMO

A 65-year-old man developed pancreatic and pubic tumors 22 years after craniotomy for a left sphenoid ridge tumor. The histological finding of the primary sphenoid ridge tumor was meningotheliomatous meningioma. The histological appearance of the biopsy specimen of the pubic tumor was hemangiopericytoma. The recurrent intracranial tumor was treated by radiosurgery, and the metastatic tumors were treated by conventional irradiation. Intracranial tumors rarely metastasize outside the central nervous system, except for meningeal hemangiopericytomas. This case indicates that meningeal hemangiopericytoma may metastasize many years after the initial onset and requires long-term follow up.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Encefálicas/diagnóstico , Hemangiopericitoma/secundário , Neoplasias Pancreáticas/secundário , Osso Púbico , Idoso , Humanos , Masculino
14.
Neurosci Lett ; 328(1): 25-8, 2002 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-12123851

RESUMO

We studied the effects of a wasp toxin beta-pompilidotoxin (beta-PMTX) on rat hippocampal CA1 interneurons by the current-clamp technique. The firing patterns of pyramidal neurons and pyramidale interneurons were not affected by beta-PMTX, but in oriens and radiatum interneurons, beta-PMTX converted the action potentials to prolonged depolarizing potentials by slowing the inactivation of Na(+) channels. In lacunosum moleculare interneurons, beta-PMTX induced initial bursting spikes followed by block of succeeding spikes. Comparison of beta-PMTX with a sea anemone toxin, ATX II, revealed that ATX II altered the firing properties of pyramidal neurons and pyramidale interneurons that were unchanged by beta-PMTX. Our results suggest that beta-PMTX modulates Na(+) currents in CA1 interneurons differently in various CA1 neurons and the toxin is useful to classify Na(+) channel subtypes.


Assuntos
Potenciais de Ação/fisiologia , Hipocampo/metabolismo , Interneurônios/metabolismo , Inibição Neural/fisiologia , Neurotoxinas/farmacologia , Células Piramidais/metabolismo , Canais de Sódio/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Venenos de Cnidários/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Proteínas de Insetos , Interneurônios/citologia , Interneurônios/efeitos dos fármacos , Masculino , Inibição Neural/efeitos dos fármacos , Vias Neurais/citologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Técnicas de Cultura de Órgãos , Células Piramidais/citologia , Células Piramidais/efeitos dos fármacos , Ratos , Ratos Wistar , Canais de Sódio/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Venenos de Vespas
15.
J Neurosci ; 22(6): 2115-24, 2002 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11896151

RESUMO

The importance of postmenopausal estrogen replacement therapy in affording protection against the selective and delayed neuronal death associated with cardiac arrest or cardiac surgery in women remains controversial. Here we report that exogenous estrogen at levels that are physiological for hormone replacement in postmenopausal women affords protection against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1 of male gerbils. Global ischemia induced a marked increase in activated caspase-3 in CA1, evident at 6 hr after ischemia. Global ischemia induced a marked upregulation of the proapoptotic neurotrophin receptor p75(NTR) in CA1, evident at 48 hr. p75(NTR) expression was induced primarily in terminal deoxynucleotidyl transferase-mediated UTP nick-end labeling-positive cells, indicating expression in neurons undergoing apoptosis. Global ischemia also induced a marked downregulation of mRNA encoding the AMPA receptor GluR2 subunit in CA1. Caspase-3, p75(NTR), and GluR2 were not significantly changed in CA3 and dentate gyrus, indicating that the ischemia-induced changes in gene expression were cell specific. Exogenous estrogen attenuated the ischemia-induced increases in activated caspase-3 and blocked the increase in p75(NTR) in post-ischemic CA1 neurons but did not prevent ischemia-induced downregulation of GluR2. These findings demonstrate that long-term estrogen at physiological levels ameliorates ischemia-induced hippocampal injury and indicate that estrogen intervenes at the level of apoptotic signaling cascades to prevent onset of death in neurons otherwise "destined to die."


Assuntos
Isquemia Encefálica/tratamento farmacológico , Estrogênios/administração & dosagem , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Isquemia Encefálica/patologia , Caspase 3 , Caspases/metabolismo , Citoproteção/efeitos dos fármacos , Regulação para Baixo , Ativação Enzimática/efeitos dos fármacos , Gerbillinae , Glutamato Descarboxilase , Hipocampo/irrigação sanguínea , Hipocampo/patologia , Hibridização In Situ , Masculino , Neurônios/enzimologia , Neurônios/patologia , RNA Mensageiro/metabolismo , Receptor de Fator de Crescimento Neural , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Regulação para Cima/efeitos dos fármacos
16.
J Neurosci Res ; 67(1): 11-20, 2002 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11754076

RESUMO

GFAP (glial fibrillary acidic protein) is an intermediate filament protein found exclusively in the astrocytes of the central nervous system. We studied the role of GFAP in the neuronal degeneration in the hippocampus after transient ischemia using knockout mice. Wild-type C57 Black/6 (GFAP(+/+)) mice and mutant (GFAP(-/-)) mice were subjected to occlusion of both carotid arteries for 5-15 min. Hippocampal slices were prepared 3 days after reperfusion and the field excitatory postsynaptic potentials (fEPSP) in the CA1 were recorded. High frequency stimulation induced robust long-term potentiation (LTP) in GFAP(-/-), as in GFAP(+/+) mice. After ischemia, however, the LTP in GFAP(-/-) was significantly depressed. Similarly, paired pulse facilitation (PPF) displayed little difference between GFAP(+/+) and GFAP(-/-), but after ischemia, the PPF in GFAP(-/-) showed a depression. Histological study revealed that loss of CA1 and CA3 pyramidal neurons after ischemia was marked in GFAP(-/-). MAP2 (dendritic) immunostaining in the post-ischemic hippocampus showed little difference but NF200 (axonal) immunoreactivity was reduced in GFAP(-/-). S100beta (glial) immunoreactivity was similar in the post-ischemic hippocampus of the GFAP(+/+) and GFAP(-/-), indicating that reactive astrocytosis did not require GFAP. Our results suggest that GFAP has an important role in astrocyte-neural interactions and that ischemic insult impairs LTP and accelerates neuronal death.


Assuntos
Astrócitos/metabolismo , Isquemia Encefálica/metabolismo , Proteína Glial Fibrilar Ácida/deficiência , Hipocampo/metabolismo , Potenciação de Longa Duração/genética , Degeneração Neural/metabolismo , Células Piramidais/metabolismo , Proteínas S100 , Animais , Astrócitos/patologia , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Morte Celular/genética , Estimulação Elétrica , Potenciais Pós-Sinápticos Excitadores/genética , Proteína Glial Fibrilar Ácida/genética , Hipocampo/patologia , Hipocampo/fisiopatologia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Degeneração Neural/genética , Degeneração Neural/patologia , Fatores de Crescimento Neural/metabolismo , Proteínas de Neurofilamentos/metabolismo , Células Piramidais/patologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Subunidade beta da Proteína Ligante de Cálcio S100 , Transmissão Sináptica/genética
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