Risk Factors of Postoperative Acute Heart Failure in Elderly Patients After Hip Fracture Surgery.

Background Postoperative acute heart failure (AHF) in elderly patients after hip fracture surgery is a common complication. Therefore, this study aimed to identify the risk factor of AHF after hip fracture surgery among the older population. Methods This retrospective cohort study was performed on 88 admitted patients whose hip fractures were fixed via internal fixation surgery in a tertiary care hospital in Rawalpindi, Pakistan, from January 2022 to March 2023. Recruitment of patients was made through established inclusion and exclusion criteria. Ethical approval and informed consent were also gained before the data collection. A self-designed form was used to collect data. Data analysis was carried out in the IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States). Both descriptive and inferential statistics were applied to compare the attributes of the patients with AHF and patients without AHF. Multivariate logistic regression was used to evaluate the association between the postoperative AHF and its potential risk factors. Results Out of 88 enrolled patients, 12 (13.64%) had developed postoperative AHF. Age ≥ 65 years (OR = 2.606, 95% CI = 1.035~4.160, p = 0.010), anemia (OR = 3.178, 95% CI = 1.847~5.990, p = 0.029), hypertension (OR = 2.019, 95% CI = 1.110~4.034, p = 0.012), diabetes mellitus (OR = 2.003, 95% CI = 1.115~4.012, p = 0.015), hypoalbuminemia (OR = 2.486, 95% CI = 1.218~4.619, p = 0.030), and operation time ≥ 120 minutes (OR = 1.702, 95% CI = 1.099~2.880, p = 0.018), were the risk factors of postoperative AHF in elderly patients after hip fracture surgery. Conclusions In the study population, the incidence of postoperative heart failure was significant and age ≥ 65 years, anemia, hypertension, diabetes mellitus, hypoalbuminemia, and operation time ≥ 120 were significantly involved in the development of it. Preoperative identification and management of AHF risk factors could lead to the prevention of postoperative complications.

Vepoloxamer improves functional recovery in rat after traumatic brain injury: A dose-response and therapeutic window study.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. There are no effective therapies available for TBI patients. Vepoloxamer is an amphiphilic polyethylene-polypropylene-polyethylene tri-block copolymer that seals membranes and restores plasma membrane integrity in damaged cells. We previously demonstrated that treatment of TBI rats with Vepoloxamer improves functional recovery. However, additional studies are needed to potentially translate Vepoloxamer treatment from preclinical studies into clinical applications. We thus conducted a study to investigate dose-response and therapeutic window of Vepoloxamer on functional recovery of adult rats after TBI. To identify the most effective dose of Vepoloxamer, male Wistar adult rats with controlled cortical impact (CCI) injury were randomly treated with 0 (vehicle), 100, 300, or 600 mg/kg of Vepoloxamer, administered intravenously (IV) at 2 h after TBI. We then performed a therapeutic window study in which the rats were treated IV with the most effective single dose of Vepoloxamer at different time points of 2 h, 4 h, 1 day, or 3 days after TBI. A battery of cognitive and neurological tests was performed. Animals were killed 35 days after TBI for histopathological analysis. Dose-response experiments showed that Vepoloxamer at all three tested doses (100, 300, 600 mg/kg) administered 2 h post injury significantly improved cognitive functional recovery, whereas Vepoloxamer at doses of 300 and 600 mg/kg, but not the 100 mg/kg dose, significantly reduced lesion volume compared to saline treatment. However, Vepoloxamer at 300 mg/kg showed significantly improved neurological and cognitive outcomes than treatment with a dose of 600 mg/kg. In addition, our data demonstrated that the dose of 300 mg/kg of Vepoloxamer administered at 2 h, 4 h, 1 day, or 3 days post injury significantly improved neurological function compared with vehicle, whereas Vepoloxamer administered at 2 h or 4 h post injury significantly improved cognitive function compared with the 1-day and 3-day treatments, with the most robust effect administered at 2 h post injury. The present study demonstrated that Vepoloxamer improves functional recovery in a dose-and time-dependent manner, with therapeutic efficacy compared with vehicle evident even when the treatment is initiated 3 days post TBI in the rat.

Molecular evidence of Ehrlichia canis, associated risk factors and hematobiochemical analysis in client owned and shelter cats of Pakistan.

Ehrlichiosis is an infectious disease caused by Ehrlichia canis (E. canis) genus and arthropod vectors. It is considered endemic in many parts of the world among dogs. But due to lack of research on cats, there isn't enough information available. The limited reports available on feline Ehrlichiosis relied on the detection of morulae in leukocytes. The current study was designed to detect the molecular prevalence of E. canis in cats along with associated risk factors and hematological analysis. A total of 384 blood samples from cats were collected from various veterinary hospitals and shelter homes and tested by microscopy and Polymerase Chain Reaction (PCR) to identify E. canis. The prevalence of E. canis has been reported at 5/384 (1.30%) and (14/384) 3.65% in cats through microscopy and PCR respectively. DNA sequences revealed significant resemblance with each other and variable resemblance with other Ehrlichia spp. sequences of different species from various countries already deposited on NCBI. Moreover, hematobiochemical and risk factor analysis were also carried out revealing significant results. This study reports first molecular detection of E. canis in client-owned and sheltered cats located in District Lahore, Punjab, Pakistan. Further studies should be conducted to identify its occurrence in the feline population of Pakistan so that control and prevention strategies must be planned accordingly. Due to the zoonotic impact of this pathogen and in perspective of one health, endemic regions of the disease should be identified and possible control measures should be implemented in these regions to minimize the spread of disease to non-endemic regions of the world and from animals to humans.

Therapeutic Role of microRNAs of Small Extracellular Vesicles from Human Mesenchymal Stromal/Stem Cells in Treatment of Experimental Traumatic Brain Injury.

Mesenchymal stem/stromal cells (MSC)-derived small extracellular vesicles (sEVs) possess therapeutic potential for treatment of traumatic brain injury (TBI). The essential role of micro ribonucleic acids (miRNAs) underlying the beneficial effects of MSC-derived sEVs for treatment of TBI remains elusive. The present study was designed to investigate the role of microRNAs in sEVs from MSCs with Argonaute 2 knockdown (Ago2-KD) in neurological recovery, neuroinflammation, and neurovascular remodeling in TBI rats. Therapeutic effects of sEVs derived from naïve MSCs (naïve-sEV), MSCs transfected with a vector carrying scramble control short hairpin RNA (shRNA; vector-sEV), and MSCs transfected with a lentiviral vector-based shRNA against Ago2 to knock down Ago2 (Ago2-KD-sEV) were determined in adult male rats subjected to a moderate TBI induced by controlled cortical impact (CCI). sEVs (naïve-sEV, vector-sEV, and Ago2-KD-sEV) or vehicle (phosphate-buffered solution [PBS]) were given intravenously 1 day post-injury (PI). Multiple neurological functional tests were performed weekly PI for 5 weeks. The Morris water maze (MWM) test was performed for spatial learning and memory 31-35 days PI. All animals were euthanized 5 weeks PI and the brains were collected for analyses of lesion volume, cell loss, neurovascular remodeling, and neuroinflammation. Ago2-KD reduced global sEV miRNA levels. Compared with the vehicle treatment, both naïve-sEV and vector-sEV treatments significantly improved functional recovery, reduced hippocampal neuronal cell loss, inhibited neuroinflammation, and promoted neurovascular remodeling (angiogenesis and neurogenesis). However, Ago2-KD-sEV treatment had a significantly less therapeutic effect on all the parameters measured above than did naïve-sEV and vector-sEV treatments. The therapeutic effects of Ago2-KD-sEV were comparable to that of vehicle treatment. Our findings demonstrate that attenuation of Ago2 protein in MSCs reduces miRNAs in MSC-derived sEVs and abolishes exosome treatment-induced beneficial effects in TBI recovery, suggesting that miRNAs in MSC-derived sEVs play an essential role in reducing neuronal cell loss, inhibiting neuroinflammation, and augmenting angiogenesis and neurogenesis, as well as improving functional recovery in TBI. The findings underscore the important role of miRNAs in MSC-derived sEVs in the treatment of TBI.

MiR-17-92 Cluster-Enriched Exosomes Derived from Human Bone Marrow Mesenchymal Stromal Cells Improve Tissue and Functional Recovery in Rats after Traumatic Brain Injury.

Exosomes play an important role in intercellular communication by delivering microribonucleic acids (miRNAs) to recipient cells. Previous studies have demonstrated that multi-potent mesenchymal stromal cell (MSC)-derived exosomes improve functional recovery after experimental traumatic brain injury (TBI). This study was performed to determine efficacy of miR-17-92 cluster-enriched exosomes (Exo-17-92) harvested from human bone marrow MSCs transfected with a miR-17-92 cluster plasmid in enhancing tissue and neurological recovery compared with exosomes derived from MSCs transfected with an empty plasmid vector (Exo-empty) for treatment of TBI. Adult male rats underwent a unilateral moderate cortical contusion. Animals received a single intravenous injection of miR-17-92 cluster-enriched exosomes (100 µg/rat, approximately 3.75x1011 particles, Exo-17-92) or control exosomes (100 µg/rat, Exo-empty) or Vehicle (phosphate-buffered solution) one day after injury. A battery of neurological functional tests was performed weekly after TBI for five weeks. Spatial learning and memory were measured on days 31-35 after TBI using the Morris water maze test. All animals were sacrificed five weeks after injury. Their brains were processed for histopathological and immunohistochemical analyses of lesion volume, cell loss, angiogenesis, neurogenesis, and neuroinflammation. Compared with Vehicle, both Exo-17-92 and Exo-empty treatments significantly improved sensorimotor and cognitive function, reduced neuroinflammation and hippocampal neuronal cell loss, promoted angiogenesis and neurogenesis without altering the lesion volume. Moreover, Exo-17-92 treatment exhibited a significantly more robust therapeutic effect on improvement in functional recovery by reducing neuroinflammation and cell loss, enhancing angiogenesis and neurogenesis than did Exo-empty treatment. Exosomes enriched with miR-17-92 cluster have a significantly better effect on improving functional recovery after TBI compared with Exo-empty, likely by reducing neuroinflammation and enhancing endogenous angiogenesis and neurogenesis. Engineering specific miRNA in exosomes may provide a novel therapeutic strategy for management of unilateral moderate cortical contusion TBI.

Mesenchymal Stem Cell-Derived Exosomes Improve Functional Recovery in Rats After Traumatic Brain Injury: A Dose-Response and Therapeutic Window Study.

Background. Mesenchymal stem cell (MSC)-derived exosomes play a critical role in regenerative medicine. Objective. To determine the dose- and time-dependent efficacy of exosomes for treatment of traumatic brain injury (TBI). Methods. Male rats were subjected to a unilateral moderate cortical contusion. In the dose-response study, animals received a single intravenous injection of exosomes (50, 100, 200 µg per rat) or vehicle, with treatment initiated at 1 day after injury. In the therapeutic window study, animals received a single intravenous injection of 100 µg exosomes or vehicle starting at 1, 4, or 7 days after injury. Neurological functional tests were performed weekly after TBI for 5 weeks. Spatial learning was measured on days 31 to 35 after TBI using the Morris water maze test. Results. Compared with the vehicle, regardless of the dose and delay in treatment, exosome treatment significantly improved sensorimotor and cognitive function, reduced hippocampal neuronal cell loss, promoted angiogenesis and neurogenesis, and reduced neuroinflammation. Exosome treatment at 100 µg per rat exhibited a significant therapeutic effect compared with the 50- or 200-µg exosome groups. The time-dependent exosome treatment data demonstrated that exosome treatment starting at 1 day post-TBI provided a significantly greater improvement in functional and histological outcomes than exosome treatments at the other 2 delayed treatments. Conclusions. These results indicate that exosomes have a wide range of effective doses for treatment of TBI with a therapeutic window of at least 7 days postinjury. Exosomes may provide a novel therapeutic intervention in TBI.

Randomized controlled trial of Cerebrolysin's effects on long-term histological outcomes and functional recovery in rats with moderate closed head injury.

OBJECTIVE: The authors previously demonstrated that Cerebrolysin is effective for treatment of mild closed head injury (CHI) when administered 4 hours after injury. The aim of this study was to determine Cerebrolysin's effects on functional and histological outcomes in rats subjected to moderate CHI. METHODS: In this randomized, blinded, and vehicle-controlled preclinical trial, male adult Wistar rats subjected to moderate CHI received either Cerebrolysin treatment at a dose of 2.5 ml/kg (n = 13) or vehicle (saline, n = 13) intraperitoneally administered daily for 10 days, starting at 4 hours after injury. Animals were subjected to cognitive and sensorimotor functional tests at multiple time points, and they were killed 3 months after injury. The brains were processed for analyses of neuronal cell loss, amyloid precursor protein, axonal damage, and neurogenesis. RESULTS: Compared with rats treated with vehicle (saline), rats treated with Cerebrolysin had significantly increased numbers of neuroblasts and newborn mature neurons in the dentate gyrus (DG) and attenuated amyloid precursor protein accumulation and axonal damage in various brain regions, as well as decreased neuronal loss in the DG and cornu ammonis 3 (CA3) region of the hippocampus (p < 0.05). Global testing using generalized estimating equations showed a significant beneficial effect of Cerebrolysin treatment on sensorimotor functional outcomes from 1 day to 3 months after injury compared to that of saline treatment (p < 0.05). Compared with vehicle-treated rats, Cerebrolysin-treated rats showed significantly and robustly improved long-term (up to 3 months) cognitive functional recovery, as measured by social interaction, Morris water maze, novel object recognition, and odor recognition tests. In the Cerebrolysin-treated rats there were significant correlations between multiple histological outcomes and functional recovery evident 3 months after moderate CHI, as indicated by Pearson partial correlation analyses. CONCLUSIONS: The authors' findings demonstrate that Cerebrolysin treatment significantly improves long-term functional and histological outcomes in rats with moderate CHI, with functional outcomes significantly correlated with histological indices of neuroplasticity and neuroprotection. These data indicate that Cerebrolysin may be useful for the treatment of moderate CHI.

Remodeling dendritic spines for treatment of traumatic brain injury.

Traumatic brain injury is an important global public health problem. Traumatic brain injury not only causes neural cell death, but also induces dendritic spine degeneration. Spared neurons from cell death in the injured brain may exhibit dendrite damage, dendritic spine degeneration, mature spine loss, synapse loss, and impairment of activity. Dendritic degeneration and synapse loss may significantly contribute to functional impairments and neurological disorders following traumatic brain injury. Normal function of the nervous system depends on maintenance of the functionally intact synaptic connections between the presynaptic and postsynaptic spines from neurons and their target cells. During synaptic plasticity, the numbers and shapes of dendritic spines undergo dynamic reorganization. Enlargement of spine heads and the formation and stabilization of new spines are associated with long-term potentiation, while spine shrinkage and retraction are associated with long-term depression. Consolidation of memory is associated with remodeling and growth of preexisting synapses and the formation of new synapses. To date, there is no effective treatment to prevent dendritic degeneration and synapse loss. This review outlines the current data related to treatments targeting dendritic spines that propose to enhance spine remodeling and improve functional recovery after traumatic brain injury. The mechanisms underlying proposed beneficial effects of therapy targeting dendritic spines remain elusive, possibly including blocking activation of Cofilin induced by beta amyloid, Ras activation, and inhibition of GSK-3 signaling pathway. Further understanding of the molecular and cellular mechanisms underlying synaptic degeneration/loss following traumatic brain injury will advance the understanding of the pathophysiology induced by traumatic brain injury and may lead to the development of novel treatments for traumatic brain injury.

Diffuse white matter response in trauma-injured brain to bone marrow stromal cell treatment detected by diffusional kurtosis imaging.

Diffuse white matter (WM) response to traumatic brain injury (TBI) and transplantation of human bone marrow stromal cells (hMSCs) after the injury were non-invasively and dynamically investigated. Male Wistar rats (300-350 g) subjected to TBI were intravenously injected with 1 ml of saline (n = 10) or with hMSCs in suspension (∼3 × 106 hMSCs, n = 10) 1-week post-TBI. MRI measurements of T2-weighted imaging and diffusional kurtosis imaging (DKI) were acquired on all animals at multiple time points up to 3-months post-injury. Functional outcome was assessed using the Morris water maze test. DKI-derived metrics of fractional anisotropy (FA), axonal water fraction (AWF) and radial kurtosis (RK) longitudinally reveal an evolving pattern of structural alteration post-TBI occurring in the brain region remote from primary impact site. The progressive structural change is characterized by gradual disruption of WM integrity at an early stage (weeks post-TBI), followed by spontaneous recovery at a later stage (months post-TBI). Transplantation of hMSCs post-TBI promotes this structural plasticity as indicated by significantly increased FA and AWF in conjunction with substantially elevated RK at the later stage. Our long-term imaging data demonstrate that hMSC therapy leads to modified temporal profiles of these metrics, inducing an earlier presence of enhanced structural remodeling, which may contribute to improved functional recovery.

A Small Molecule Spinogenic Compound Enhances Functional Outcome and Dendritic Spine Plasticity in a Rat Model of Traumatic Brain Injury.

The tetra (ethylene glycol) derivative of benzothiazole aniline (SPG101) has been shown to improve dendritic spine density and cognitive memory in the triple transgenic mouse model of Alzheimer disease (AD) when administered intraperitoneally. The present study was designed to investigate the therapeutic effects of SPG101 on dendritic spine density and morphology and sensorimotor and cognitive functional recovery in a rat model of traumatic brain injury (TBI) induced by controlled cortical impact (CCI). Young adult male Wistar rats with CCI were randomly divided into the following two groups (n = 7/group): (1) Vehicle, and (2) SPG101. SPG101 (30 mg/kg) dissolved in vehicle (1% dimethyl sulfoxide in phosphate buffered saline) or Vehicle were intraperitoneally administered starting at 1 h post-injury and once daily for the next 34 days. Sensorimotor deficits were assessed using a modified neurological severity score and adhesive removal and foot fault tests. Cognitive function was measured by Morris water maze, novel object recognition (NOR), and three-chamber social recognition tests. The animals were sacrificed 35 days after injury, and their brains were processed for measurement of dendritic spine density and morphology using ballistic dye labeling. Compared with the vehicle treatment, SPG101 treatment initiated 1 h post-injury significantly improved sensorimotor functional recovery (days 7-35, p < 0.0001), spatial learning (days 32-35, p < 0.0001), NOR (days 14 and 35, p < 0.0001), social recognition (days 14 and 35, p < 0.0001). Further, treatment significantly increased dendritic spine density in the injured cortex (p < 0.05), decreased heterogeneous distribution of spine lengths in the injured cortex and hippocampus (p < 0.0001), modifications that are associated with the promotion of spine maturation in these brain regions. In summary, treatment with SPG101 initiated 1 h post-injury and continued for an additional 34 days improves both sensorimotor and cognitive functional recovery, indicating that SPG101 acts as a spinogenic agent and may have potential as a novel treatment of TBI.

Cerebrolysin Reduces Astrogliosis and Axonal Injury and Enhances Neurogenesis in Rats After Closed Head Injury.

BACKGROUND: Cerebrolysin is a neuropeptide preparation with neuroprotective and neurotrophic properties. Our previous study demonstrates that cerebrolysin significantly improves functional recovery in rats after mild traumatic brain injury (mTBI). OBJECTIVE: To determine histological outcomes associated with therapeutic effects of cerebrolysin on functional recovery after TBI. METHODS: In this prospective, randomized, blinded, and placebo-controlled study, adult Wistar rats with mild TBI induced by a closed head impact were randomly assigned to one of the cerebrolysin dose groups (0.8, 2.5, 7.5 mL/kg) or placebo, which were administered 4 hours after TBI and then daily for 10 consecutive days. Functional tests assessed cognitive, behavioral, motor, and neurological performance. Study end point was day 90 after TBI. Brains were processed for histological tissue analyses of astrogliosis, axonal injury, and neurogenesis. RESULTS: Compared with placebo, cerebrolysin significantly reduced amyloid precursor protein accumulation, astrogliosis, and axonal damage in various brain regions and increased the number of neuroblasts and neurogenesis in the dentate gyrus. There was a significant dose effect of cerebrolysin on functional outcomes at 3 months after injury compared with saline treatment. Cerebrolysin at a dose of ⩾0.8 mL/kg significantly improved cognitive function, whereas at a dose of ⩾2.5 mL/kg, cerebrolysin also significantly improved sensorimotor function at various time points. There were significant correlations between multiple histological and functional outcomes 90 days after mTBI. CONCLUSIONS: Our findings demonstrate that cerebrolysin reduces astrogliosis and axonal injury and promotes neurogenesis, which may contribute to improved functional recovery in rats with mTBI.

Molecular detection of Ehrlichia canis in dogs from three districts in Punjab (Pakistan).

Canine monocytic ehrlichiosis is a tick-borne disease caused by an intracellular alpha-proteobacterium, Ehrlichia canis, which replicates within mononuclear cells in the host. This study was designed to use a polymerase chain reaction (PCR) protocol for the molecular detection of E. canis by the amplification of a portion of its 16S rRNA gene, as well as the effects of this alpha-proteobacterium on the haematological parameters of the sampled dogs and the risk factors associated with E. canis infection. A total of 151 blood samples were collected from dogs of various breeds at three sampling sites (Lahore, Rawalpindi/Islamabad and Multan) in Punjab, Pakistan. Data regarding the epidemiological factors (including age, gender, breed, body temperature, deworming, vaccination, mucous membrane status, hydration status, the presence of haematuria and tick infestation) were collected through a questionnaire at the time of sample collection. A 400 bp DNA fragment of the 16S rRNA gene of E. canis was amplified from 42 dog blood samples (28% of the total), [Lahore (N = 24), Rawalpindi/Islamabad (N = 13) and Multan (N = 05)] through PCR. Data analysis revealed that the character of the animals (age, sex and breed) had no significant association (P > 0.05) with the presence of E. canis. Various haematological parameters were also compared, and the results revealed that all of the parameters remained unaffected, except significantly lower white blood cell counts (P = 0.004) in E. canis-positive blood samples, as compared with the control group. We concluded that this is the first molecular confirmation of canine infection by E. canis using PCR. Moreover, no specific epidemiological parameter was found associated with the prevalence of E. canis in dogs.

Current understanding of neuroinflammation after traumatic brain injury and cell-based therapeutic opportunities.

Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death. TBI is not just an acute event but a chronic disease. Among many mechanisms involved in secondary injury after TBI, emerging preclinical studies indicate that posttraumatic prolonged and progressive neuroinflammation is associated with neurodegeneration which may be treatable long after the initiating brain injury. This review provides an overview of recent understanding of neuroinflammation in TBI and preclinical cell-based therapies that target neuroinflammation and promote functional recovery after TBI.

Prospective, randomized, blinded, and placebo-controlled study of Cerebrolysin dose-response effects on long-term functional outcomes in a rat model of mild traumatic brain injury.

Using a prospective, randomized, blinded, placebo-controlled protocol, the authors demonstrated that Cerebrolysin at doses of 0.8-7.5 ml/kg, administered 4 hours after injury and then once daily for a total of 10 consecutive days, improves long-term functional outcomes in a rat model of mild closed head injury; a 2.5-ml/kg dose was identified as optimal. These findings suggest that Cerebrolysin has the potential to treat mild traumatic brain injury, the incidence of which is high without effective treatments.

Treatment of Traumatic Brain Injury with Vepoloxamer (Purified Poloxamer 188).

Vepoloxamer is an amphipathic polymer that has shown potent hemorrheologic, cytoprotective, and anti-inflammatory effects in both pre-clinical and clinical studies. This study was designed to investigate the therapeutic effects of vepoloxamer on sensorimotor and cognitive functional recovery in rats after traumatic brain injury (TBI) induced by controlled cortical impact. Young adult male Wistar rats were randomly divided into the following groups: 1) sham; 2) saline; or 3) vepoloxamer. Vepoloxamer (300 mg/kg) or saline was administered over 60 min via intravenous infusion into tail veins starting at 2 h post-injury. Sensorimotor function and spatial learning were assessed using a modified neurological severity score and foot fault test, and Morris water maze test, respectively. The animals were sacrificed 35 days after injury and their brains were processed for measurement of lesion volume and neuroinflammation. Compared with the saline treatment, vepoloxamer initiated 2 h post-injury significantly improved sensorimotor functional recovery (Days 1-35; p < 0.0001) and spatial learning (Days 32-35; p < 0.0001), reduced cortical lesion volume by 20%, and reduced activation of microglia/macrophages and astrogliosis in many brain regions including injured cortex, corpus callosum, and hippocampus, as well as normalized the bleeding time and reduced brain hemorrhage and microthrombosis formation. In summary, vepoloxamer treatment initiated 2 h post-injury provides neuroprotection and anti-inflammation in rats after TBI and improves functional outcome, indicating that vepoloxamer treatment may have potential value for treatment of TBI. Further investigation of the optimal dose and therapeutic window of vepoloxamer treatment for TBI and the mechanisms underlying beneficial effects are warranted.

Traumatic pneumocephaly: trapped air from where?

Traumatic pneumocephaly is literally defined as 'air in the head' after trauma. While this phenomenon has been well described in the literature, our case report is unique in describing diffuse pneumocephalus in the subaponeurotic space, subdural space, subarachnoid space, brain and ventricles without a break in the cranial vault: a 26-year-old man fell from a =9 meter scaffolding in a water tower. Following an arduous and delayed extrication, the patient was unresponsive with loss of pulse requiring intubation, cardiopulmonary resuscitation and release of tension pneumothorax with bilateral thoracostomy tubes. Examination remained poor with a Glasgow Coma Scale of 3. Immediate exploratory laparotomy was performed for a small right retroperitoneal haematoma on Focused Assessment with Sonography for Trauma. Postoperative imaging revealed diffuse pneumocephaly without facial fractures. This case presentation explores unusual causes of fistulous connections with the atmosphere that may lead to air trapped in and around the cranial vault.

Chronic global analysis of vascular permeability and cerebral blood flow after bone marrow stromal cell treatment of traumatic brain injury in the rat: A long-term MRI study.

Vascular permeability and hemodynamic alteration in response to the transplantation of human bone marrow stromal cells (hMSCs) after traumatic brain injury (TBI) were longitudinally investigated in non directly injured and normal-appearing cerebral tissue using magnetic resonance imaging (MRI). Male Wistar rats (300-350g, n=30) subjected to controlled cortical impact TBI were intravenously injected with 1ml of saline (at 6-h or 1-week post-injury, n=5/group) or with hMSCs in suspension (∼3×106 hMSCs, at 6-h or 1-week post-injury, n=10/group). MRI measurements of T2-weighted imaging, cerebral blood flow (CBF) and blood-to-brain transfer constant (Ki) of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), and neurological behavioral estimates were performed on all animals at multiple time points up to 3-months post-injury. Our long-term imaging data show that blood-brain barrier (BBB) breakdown and hemodynamic disruption after TBI, as revealed by Ki and CBF, respectively, affect both hemispheres of the brain in a diffuse manner. Our data reveal a sensitive vascular permeability and hemodynamic reaction in response to the time-dependent transplantation of hMSCs. A more rapid reduction of Ki following cell treatment is associated with a higher level of CBF in the injured brain, and acute (6h) cell administration leads to enhanced therapeutic effects on both the recovery of vascular integrity and stabilization of cerebral perfusion compared to delayed (1w) cell engraftment. Our results indicate that cell-enhanced BBB reconstitution plays an important role in underlying the restoration of CBF in the injured brain, which in turn, contributes to the improvement of functional outcome.

Chronic thoracolumbar subdural empyema: Case report and surgical management.

BACKGROUND: Spinal cord abscesses and spinal subdural empyemas are rare and difficult to treat. CASE DESCRIPTION: A 35-year-old male presented to an outside institution with 2 months of progressive low back pain, weakness, and bowel incontinence; he was diagnosed with an L4 epidural abscess that was poorly managed. When the patient presented to our institution, magnetic resonance imaging (MRI) revealed a well-organized chronic subdural abscess at the thoracolumbar junction. Following resection, his back pain resolved but he was left with a residual paraparesis. CONCLUSION: Subdural abscesses are rare and should be considered among the differential diagnoses for intraspinal mass lesions. Treatment should include prompt surgical exploration and decompression combined with appropriate prolonged antibiotic treatment.

Emerging potential of exosomes for treatment of traumatic brain injury.

Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. No effective treatment has been identified from clinical trials. Compelling evidence exists that treatment with mesenchymal stem cells (MSCs) exerts a substantial therapeutic effect after experimental brain injury. In addition to their soluble factors, therapeutic effects of MSCs may be attributed to their generation and release of exosomes. Exosomes are endosomal origin small-membrane nano-sized vesicles generated by almost all cell types. Exosomes play a pivotal role in intercellular communication. Intravenous delivery of MSC-derived exosomes improves functional recovery and promotes neuroplasticity in rats after TBI. Therapeutic effects of exosomes derive from the exosome content, especially microRNAs (miRNAs). miRNAs are small non-coding regulatory RNAs and play an important role in posttranscriptional regulation of genes. Compared with their parent cells, exosomes are more stable and can cross the blood-brain barrier. They have reduced the safety risks inherent in administering viable cells such as the risk of occlusion in microvasculature or unregulated growth of transplanted cells. Developing a cell-free exosome-based therapy may open up a novel approach to enhancing multifaceted aspects of neuroplasticity and to amplifying neurological recovery, potentially for a variety of neural injuries and neurodegenerative diseases. This review discusses the most recent knowledge of exosome therapies for TBI, their associated challenges and opportunities.