Journal of neurotrauma
-
Journal of neurotrauma · Apr 2013
Comparative StudySimilarities and differences of acute nonconvulsive seizures and other epileptic activities following penetrating and ischemic brain injuries in rats.
The similarities and differences between acute nonconvulsive seizures (NCS) and other epileptic events, for example, periodic epileptiform discharges (PED) and intermittent rhythmic delta activities (IRDA), were characterized in rat models of penetrating and ischemic brain injuries. The NCS were spontaneously induced by either unilateral frontal penetrating ballistic-like brain injury (PBBI) or permanent middle cerebral artery occlusion (pMCAO), and were detected by continuous electroencephalogram (EEG) monitoring begun immediately after the injury and continued for 72 h or 24 h, respectively. Analysis of NCS profiles (incidence, frequency, duration, and time distribution) revealed a high NCS incidence in both injury models. ⋯ By contrast, the IRDA appeared to be independent of other epileptic events. This study provided comprehensive comparisons of post-traumatic and post-ischemic epileptic profiles. The identification of the similarities and differences across a broad spectrum of epileptic events may lead to differential strategies for post-traumatic and post-stroke seizure interventions.
-
Journal of neurotrauma · Apr 2013
Donepezil is ineffective in promoting motor and cognitive benefits after controlled cortical impact injury in male rats.
The acetylcholinesterase (AChE) inhibitor donepezil is used as a therapy for Alzheimer's disease and has been recommended as a treatment for enhancing attention and memory after traumatic brain injury (TBI). Although select clinical case studies support the use of donepezil for enhancing cognition, there is a paucity of experimental TBI studies assessing the potential efficacy of this pharmacotherapy. Hence, the aim of this pre-clinical study was to evaluate several doses of donepezil to determine its effect on functional outcome after TBI. ⋯ Moreover, the two highest doses significantly impaired beam-balance (3.0 mg/kg), beam-walk (2.0 mg/kg and 3.0 mg/kg), and cognitive performance (3.0 mg/kg) versus vehicle. These data indicate that chronic administration of donepezil is not only ineffective in promoting functional improvement after moderate CCI injury, but depending on the dose is actually detrimental to the recovery process. Further work is necessary to determine if other AChE inhibitors exert similar effects after TBI.
-
Journal of neurotrauma · Apr 2013
Monitoring functional impairment and recovery after traumatic brain injury in rats by FMRI.
The present study was designed to test a hypothesis that functional magnetic resonance imaging (fMRI) can be used to monitor functional impairment and recovery after moderate experimental traumatic brain injury (TBI). Moderate TBI was induced by lateral fluid percussion injury in adult rats. The severity of brain damage and functional recovery in the primary somatosensory cortex (S1) was monitored for up to 56 days using fMRI, cerebral blood flow (CBF) by arterial spin labeling, local field potential measurements (LFP), behavioral assessment, and histology. ⋯ This is, to our knowledge, the first study demonstrating that fMRI can be used to monitor post-TBI functional impairment and consequent spontaneous recovery. Moreover, the BOLD response was associated with the density of myelinated fibers in the S1, rather than with neurodegeneration. The present findings encourage exploration of the usefulness of fMRI as a noninvasive prognostic biomarker for human post-TBI outcomes and therapy responses.
-
Journal of neurotrauma · Apr 2013
Poloxamer 188 attenuates in vitro traumatic brain injury-induced mitochondrial and lysosomal membrane permeabilization damage in cultured primary neurons.
Acute membrane damage due to traumatic brain injury (TBI) is a critical precipitating event. However, the subsequent effects of the mechanical trauma, including mitochondrial and lysosomal membrane permeability (MOMP and LMP) remain elusive. The main objective of the current study was to assess the role of a putative membrane-resealing agent poloxamer 188 (P188) in MOMP and LMP in response to a well-defined mechanical insult. ⋯ Both P188 and CBI treatment decreased the cytosolic accumulation of tBid in supernatant of purified lysosomes, and the amount of mitochondrial localized tBid. These data indicate injured neurons have undergone mitochondrial and lysosomal membrane permeability damage, and the mechanism can be exploited with pharmacological interventions. P188's neuroprotection appears to involve a relationship between cathepsin B and tBid-mediated mitochondrial initiation of cell death.
-
Journal of neurotrauma · Apr 2013
Effects of topical administration of nimodipine on cerebral blood flow following subarachnoid hemorrhage in pigs.
We sought to explore whether topical administration of nimodipine improves the abnormal cerebral perfusion following subarachnoid hemorrhage (SAH) in pigs. Fourteen pigs were randomly divided into three groups: sham (n=4), SAH (n=5), or SAH + nimodipine (n=5). The SAH model was established by injecting fresh autologous nonheparinized arterial blood into the suprasellae cistern. ⋯ Topical administration of nimodipine did not significantly improve CBF following SAH. These findings were not consistent with our previous data demonstrating that the topical administration of nimodipine significantly alleviates cerebral vasospasm following SAH detected by TCD. Potential mechanisms governing these disparate outcomes require further investigation.