Journal of neurotrauma
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Journal of neurotrauma · Feb 2017
Blood aggravates histological and functional damage after acute subdural hematoma in rats.
Acute subdural hematoma (ASDH) is associated with high morbidity and mortality. Whether the volume effect of the hematoma and increase of intracranial pressure (ICP) or the local effect of blood are responsible for this severe pathophysiology is unclear. Therefore, we compared subdural infusion of autologous blood and paraffin oil in a rat model of ASDH. ⋯ In the behavioral evaluation, paraffin-infused animals showed a better recovery, compared with the blood infusion group. In conclusion, comparable acute time-course of ICP, CPP, and CBF clearly indicates that the differences in lesion size, inflammatory reaction, and behavioral deficits after blood- and paraffin oil-induced ASDH are partially due to blood constituents. Therefore, current data suggest that subdural hematomas should be completely removed as quickly as possible; decompression alone may not be sufficient to prevent secondary brain damage.
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Journal of neurotrauma · Feb 2017
Memantine reduced cell death, astrogliosis, and functional deficits in an in vitro model of repetitive mild traumatic brain injury.
Clinical studies suggest that athletes with a history of concussion may be at risk for additional mild traumatic brain injury (mTBI), and repetitive exposure to mTBI acutely increases risk for more significant and persistent symptoms and increases future risk for developing neurodegenerative diseases. Currently, symptoms of mTBI are managed with rest and pain medication; there are no drugs approved by the Food and Drug Administration (FDA) that target the biochemical pathology underlying mTBI to treat or prevent acute and long-term effects of repetitive mTBI. Memantine is an FDA-approved drug for treating Alzheimer's disease, and also was shown to be neuroprotective in rodents following a single, moderate to severe TBI. ⋯ Samples received two injuries 24 h apart; injury resulted in significant cell death, loss of long-term potentiation (LTP), and astrogliosis compared with naïve, uninjured samples. Delivery of 1.5 μM memantine 1 h following each stretch significantly reduced the effect of injury for all outcome measures, and did not alter those outcome measures that were unaffected by the injury. Therefore, memantine warrants further pre-clinical and clinical investigation for its therapeutic efficacy to prevent cognitive deficits and neuropathology from multiple mTBIs.
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Journal of neurotrauma · Feb 2017
Apolipoprotein E Mimetic Peptide Increases Cerebral Glucose Uptake by Relieving Blood Brain Barrier Disruption Following Controlled Cortical Impact in Mice: An 18F-fluorodeoxyglucose PET/CT Study.
Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB) and reduces cerebral glucose uptake. Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI, and COG1410 has demonstrated neuroprotective activity in several models of TBI. However, the effects of COG1410 on VEGF and glucose metabolism following TBI are unknown. ⋯ The results showed that controlled cortical impact (CCI)-induced vestibulomotor deficits were accompanied by increases in brain edema and the expression of VEGF, with a decrease in cerebral glucose uptake. COG1410 treatment significantly improved vestibulomotor deficits and glucose uptake and produced decreases in VEGF in the pericontusion and ipsilateral hemisphere of injury, as well as in brain edema and neuronal degeneration compared with the control group. These data support that COG1410 may have potential as an effective drug therapy for TBI.
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Journal of neurotrauma · Feb 2017
Neuropsychiatric symptom modeling in male and female C57BL/6J mice following experimental traumatic brain injury.
Psychiatric symptoms such as anxiety and depression are frequent and persistent complaints following traumatic brain injury (TBI). Modeling these symptoms in animal models of TBI affords the opportunity to determine mechanisms underlying behavioral pathologies and to test potential therapeutic agents. However, testing these symptoms in animal models of TBI has yielded inconsistent results. ⋯ Increased levels of activity were also measured in female mice and injured mice in these tests, and conclusions regarding anxiety should be taken with caution when experimental manipulations induce changes in baseline activity. These results underscore the irreconcilability of results from studies attempting to model TBI-induced neuropsychiatric symptoms. Changes in injury models or better attempts to replicate the clinical syndrome may improve the translational applicability of rodent models of TBI-induced anxiety and depression.
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Journal of neurotrauma · Feb 2017
Disruption of locomotion in response to hindlimb muscle stretch at acute and chronic time points after a spinal cord injury in rats.
After spinal cord injury (SCI) muscle contractures develop in the plegic limbs of many patients. Physical therapists commonly use stretching as an approach to avoid contractures and to maintain the extensibility of soft tissues. We found previously that a daily stretching protocol has a negative effect on locomotor recovery in rats with mild thoracic SCI. ⋯ The current study extends our observations of the stretching phenomenon to a more clinically relevant moderately severe SCI animal model. The results are in agreement with our previous findings and further demonstrate that spinal cord locomotor circuitry is especially vulnerable to the negative effects of stretching at chronic time points. While the clinical relevance of this phenomenon remains unknown, we speculate that stretching may contribute to the lack of locomotor recovery in some patients.