Journal of neurotrauma
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Journal of neurotrauma · Apr 1997
Effects of the novel NMDA antagonists CP-98,113, CP-101,581 and CP-101,606 on cognitive function and regional cerebral edema following experimental brain injury in the rat.
The present study evaluated the effects of two novel N-methyl-D-aspartate (NMDA) receptor blockers and ifenprodil derivatives, CP-101,606 and CP-101,581, and their racemic mixture CP-98,113, on spatial memory and regional cerebral edema following experimental fluid-percussion (FP) brain injury in the rat (n = 66). Fifteen minutes after brain injury (2.5 atm), animals received either (1) CP-98,113 (5 mg/kg, i.p., n = 11), (2) CP-101,581 (5 mg/kg, i.p., n = 13), (3) CP-101,606 (6.5 mg/kg, i.p., n = 12), or (4) DMSO vehicle (equal volume, n = 12); followed by a continuous 24-h subcutaneous infusion of drug at a rate of 1.5 mg/kg/h by means of miniature osmotic (Alzet) pumps implanted subcutaneously. Control (uninjured) animals were subjected to identical anesthesia and surgery without injury and received DMSO vehicle (n = 8); CP-98,113 (5 mg/kg, i.p., n = 3); CP-101,581 (5 mg/kg, i.p., n = 3); or CP-101,606 (6.5 mg/kg, i.p., n = 3). ⋯ Administration of either CP-98,113, CP-101,581, or CP-101,606 had no effect on sham (uninjured) animals, but significant attenuated spatial memory impairment assessed at 2 days postinjury (p = 0.004, p = 0.02, or p = 0.02, respectively). Administration of CP-89,113 but not CP-101,581 or CP-101,606 significantly reduced the extent of regional cerebral edema in the cortex adjacent to the site of injury (p < 0.05) and in the ipsilateral hippocampus (p < 0.05) and thalamus (p < 0.05). These results suggest that excitatory neurotransmission may play a pivotal role in the pathogenesis of memory dysfunction following traumatic brain injury (TBI) and that blockade of the NMDA receptor may significantly attenuate cognitive deficits associated with TBI.
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Journal of neurotrauma · Mar 1997
Serial recording of somatosensory and myoelectric motor evoked potentials: role in assessing functional recovery after graded spinal cord injury in the rat.
Accurate functional outcome measures are essential in assessing therapeutic interventions after experimental spinal cord injury (SCI). We examined the hypothesis that serial recording of somatosensory (SSEP) and myoelectric motor evoked potentials (mMEPs) would provide complementary information to standard methods of behavioral analysis in a rat model of SCI and would allow objective discrimination of functional recovery in sensory and motor tracts. Clip compression injury of varying severity (sham, 23 g, 34 g, 56 g) and transections were performed at T1 in adult rats. ⋯ The tibialis anterior mMEP correlated significantly, though weakly, with changes in inclined plane (R = 0.49) and Tarlov scores (R = 0.41). Although the mMEPs were sensitive to the presence of SCI, these recordings did not discriminate between severities of injury. We conclude that serial recording of SSEPs but not myoelectric MEPs correlates closely with the extent and temporal course of clinical neurological recovery after graded SCI in the rat.
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Journal of neurotrauma · Feb 1997
Motor and cognitive functional deficits following diffuse traumatic brain injury in the immature rat.
To determine the motor and cognitive deficits following a diffuse severe traumatic brain injury (TBI) in immature Sprague Dawley rats (17 days), four groups of animals were injured at different severity levels using a new closed head weight drop model: (sham, severe injury [SI: 100 g/2 m], SH [SI + hypoxemia (30 min of an FiO2 of 8% posttrauma)], and ultra severe injury [US: 150 g/2 m]). Latency on beam balance, grip test performance, and maintenance of body position on an inclined board were measured daily after injury to assess vestibulomotor function. Cognitive function was assessed on days 11-22 using the Morris water maze (MWM). ⋯ US, however, produced significant cognitive dysfunction (vs. sham, SI, and SH), specifically, greater latencies to find the hidden platform through 22 days. Swim speeds were not significantly different between any of the injury groups and shams. These data indicate that (1) beam balance, inclined plane and MWM techniques are useful for assessing motor and cognitive function after TBI in immature rats; (2) SI produces motor but not cognitive deficits, which was not augmented by transient hypoxia; and (3) US created a marked but reversible motor deficit up to 10 days, and a sustained cognitive dysfunction for up to 22 days after TBI.
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Journal of neurotrauma · Jan 1997
Metabolic quantification of lesion volume following experimental traumatic brain injury in the rat.
A reliable and rapid method for quantifying lesion volume following traumatic brain injury (TBI) has vast potential in brain injury research. Staining with 2, 3, 5-triphenyltetrazolium chloride (TTC) provides for demarcation of damaged or infarcted tissue from normal, viable cerebral tissue, in which a red formazan product is formed by reduction during cellular respiration of mitochondrial dehydrogenase enzymes. The present study evaluated the use of TTC staining to quantify the cortical lesion volume in rats undergoing fluid-percussion (FP) brain injury. ⋯ The mean (+/-SD) lesion volumes were 12.1 (+/-4.5) mm3 following mild injury, 33.8 (+/-8.6) mm3 following moderate injury, and 45.1 (+/-14.0) mm3 following severe injury. A significant difference was observed between all injury groups using a t test with Bonferroni correction (p < 0.05). These results suggest that the TTC staining technique is a useful, rapid, and reproducible method for quantification of lesion volume following lateral FP brain injury.
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Journal of neurotrauma · Dec 1996
Riluzole, a novel neuroprotective agent, attenuates both neurologic motor and cognitive dysfunction following experimental brain injury in the rat.
Several potential mechanisms are involved in mediating the pathophysiology of traumatic brain injury (TBI), including inflammatory processes and excitotoxicity. In the present study, we evaluated the ability of the use-dependent sodium channel inhibitor Riluzole to attenuate cognitive and neurologic motor deficits and reduce regional cerebral edema and histologic cell damage following lateral fluid-percussion (FP) brain injury in rats (n = 109). In study 1, 58 anesthetized male Sprague-Dawley rats (350-400 g) were subjected to FP brain injury of moderate severity (2.3-2.5 atm). ⋯ In study 3, brain-injured animals were treated with Riluzole (8 mg/kg x 3 doses, n = 10) or vehicle (n = 10), and posttraumatic lesion volume was assessed at 48 h postinjury using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Treatment with Riluzole had no significant effect on posttraumatic lesion volume. The present study demonstrates that use-dependent sodium channel inhibitors, such as Riluzole, can attenuate both cognitive and neuromotor dysfunction associated with brain trauma.