Biomedical subjects

B G Lyeth

Publications and source records attributed to B G Lyeth.

At least 37 records · Page 2Linked to original sources

PubMed1996

Voltage-dependent Na+/K+ ion channel blockade fails to ameliorate behavioral deficits after traumatic brain injury in the rat.

Traumatic brain injury (TBI) induces massive, transient ion flux, after impact. This may be via agonist gated channels, such as the muscarinic, cholinergic or NMDA receptor, or via voltage-dependent channels. Pharmacological blockade of the former, is neuroprotective in most TBI models, but the role of voltage-dependent Na+/K+ channels has not been tested. We have therefore tested the hypothesis that intraventricular tetrodotoxin (TTX) (20 microliters, 5 mM) induced blockade of post-TBI ion flux will prevent cytotoxic cell swelling, Na+ and K+ flux, and behavioral deficit. Microdialysis demonstrated blockade of [K+]d flux in the TTX group compared to controls. Behavioral evaluation of motor (days 1-5) and memory function (days 11-15) after TBI revealed no beneficial effect in the TTX group compared to controls. Thus, although evidence of reduced ionic flux was demonstrated in the TTX group, memory and behavior were unaffected, suggesting that agonist-operated channel-mediated ion flux is more important after TBI.

Animals↗

PubMed1995

Metabotropic glutamate antagonist, MCPG, treatment of traumatic brain injury in rats.

The metabotropic glutamate receptor (mGluR) antagonist, alpha-methyl-4-carboxyphenylglycine (MCPG) was administered into the left lateral ventricle 5 min prior to fluid percussion traumatic brain injury (TBI) in the rat. A single 5.0 microliters ventricular infusion of the active isomer. (+)-MCPG (0.2 mumol), significantly reduced beam walking motor deficits on days 1-5 after injury and learning/memory deficits measured on days 11-15 after injury. Neither a lower dose of (+)-MCPG (0.2 mumol) affected behavioral outcome. (+)-MCPG (0.2 mumol) did not affect systemic hemodynamic responses to injury. These results suggest that TBI induced activation of mGluRs contributes to behavioral morbidity and that blockade of certain mGluR subtypes (mGluR1, mGluR5 and/or mGluR2) may reduce these pathophysiological responses.

Analysis of Variance↗

PubMed1995

The effect of postinjury kindled seizures on cognitive performance of traumatically brain-injured rats.

The purpose of this experiment was to examine the consequences of postinjury seizures on cognitive performance after experimental traumatic brain injury (TBI). Rats either were injured at a moderate (2.1 atm) level of central fluid percussion TBI (n = 16) or were surgically prepared but did not receive a fluid pulse (sham-injured control, n = 16). Beginning 24 h after TBI, injured animals were injected (ip) once daily (Days 1-24 postinjury) with either saline (n = 8) or 25 mg/kg pentylenetetrazol (PTZ) (n = 8). Sham-injured rats were injected with an equal volume of saline (n = 8) or PTZ (n = 8). In both injured and sham-injured animals, daily injections of PTZ resulted in an increase in the severity of behavioral seizures over days. On Days 25-29 after injury or sham injury, all animals were tested in the Morris water maze (MWM). Analysis of maze performance indicated that in sham-injured animals PTZ-produced seizures had a detrimental effect on performance. In injured animals, however, PTZ-treated animals exhibited significantly faster acquisition and better terminal performance in the MWM than did untreated injured animals. These results show that posttraumatic kindled seizures do not exacerbate behavioral deficits after TBI and may, in fact, improve recovery following injury. The findings of this experiment are consistent with the hypothesis that post-TBI neuronal depression may contribute to behavioral morbidity following injury.

Animals↗

PubMed1995

Long-term potentiation deficits and excitability changes following traumatic brain injury.

The effects of traumatic brain injury (TBI) on hippocampal long-term potentiation (LTP) and cellular excitability were assessed at postinjury days 2, 7, and 15. TBI was induced using a well-characterized central fluid-percussion model. LTP of the Schaffer collateral/commissural system was assessed in vivo in urethane-anesthetized rats. Significant LTP of the population excitatory postsynaptic potential (EPSP) slope was found only in controls, and no recovery to control levels was observed for any postinjury time point. Four measurement parameters reflecting pyramidal cell discharges (population spike) indicated that TBI significantly increased cellular excitability at postinjury day 2: (1) pretetanus baseline recording showed that TBI reduced population spike threshold and latency; (2) tetanic stimulation (400 Hz) increased population spike amplitudes to a greater degree in injured animals than in control animals; (3) tetanus-induced population spike latency shifts were greater in injured cases; and (4) tetanic stimulation elevated EPSP to spike ratios (E-S potentiation) to a greater degree in injured animals. These parameters returned to control levels, as measured on postinjury days 7 and 15. These results suggest that TBI-induced excitability changes persist at least through 2 days postinjury and involve a differential impairment of mechanisms subserving LTP of synaptic efficacy and mechanisms related to action potential generation.

Action Potentials↗

PubMed1995

Differential modulation of carbachol and trans-ACPD-stimulated phosphoinositide turnover following traumatic brain injury.

In the fluid percussion model of traumatic brain injury (TBI), we examined muscarinic and metabotropic glutamate receptor-stimulated polyphosphoinositide (PPI) turnover in rat hippocampus. Moderate injury was obtained by displacement and deformation of the brain within the closed cranial cavity using a fluid percussion device. Carbachol and (+/-)-1-Aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD)-stimulated PPI hydrolysis was assayed in hippocampus from injured and sham-injured controls at both 1 hour and 15 days following injury. At 1 hour after TBI, the response to carbachol was enhanced in injured rats by up to 200% but the response to trans-ACPD was diminished by as much as 28%. By contrast, at 15 days after TBI, the response to carbachol was enhanced by 25% and the response to trans-ACPD was enhanced by 73%. The ionotropic glutamate agonists N-methyl-D-aspartate (NMDA), and alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionate (AMPA), did not increase PPI hydrolysis in either sham or injured rats and injury did not alter basal hydrolysis. Thus, hippocampal muscarinic and metabotropic receptors linked to phospholipase C are differentially altered by TBI.

Animals↗

PubMed1995

Effects of mu opioid agonist and antagonist on neurological outcome following traumatic brain injury in the rat.

We examined the effects of an exogenous mu opioid agonist and antagonist on systemic physiology and neurological outcome following TBI in the rat. Experiment I: [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) (0.1 nMol or 0.3 nMol in 5 microliters) (n = 10) or artificial CSF (n = 10) was administered 5 min prior to fluid-percussion brain injury (2.1 atmospheres). Motor performance was assessed on days 1-5 after TBI. The mu receptor agonist, DAMGO significantly reduced both beam-walking latency and body weight loss after injury (p < 0.05). DAMGO-treated rats (n = 5) did not differ from CSF-treated rats (n = 5) on either systemic arterial blood pressure or heart rate responses to injury. Experiment II: Beta-funaltrexamine (beta-FNA) (20.0 nMol in 5.0 microliters) (n = 10) or artificial CSF (n = 10) was administered (icv) to rats 5 min prior to fluid-percussion brain injury (1.8 atmospheres). Motor performance was assessed on days 1-5 after TBI. The mu receptor antagonist, beta-FNA, significantly increased beam-walking latency after injury (p < 0.05). beta-FNA-treated rats (n = 5) did not differ from CSF-treated rats (n = 5) on either systemic arterial blood pressure or heart rate responses to injury. Experiment III: Neither beta-FNA nor DAMGO affected motor performance in uninjured rats. These results suggest that activation of mu opioid receptors by exogenous agonists may provide protection against deficits in motor performance produced by fluid percussion brain injury.

Animals↗

PubMed1995

Differential consequences of lateral and central fluid percussion brain injury on receptor coupling in rat hippocampus.

We have identified alterations in the responses of muscarinic and metabotropic receptors in rat hippocampus that persist for at least 15 days after central fluid percussion injury. This study compares the effect of lateral fluid percussion and central fluid percussion on these responses. Moderate injury was obtained by displacement and deformation of the brain within the closed cranial cavity using a fluid percussion device positioned either centrally or laterally. Carbachol and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD)-stimulated polyphosphoinositide (PPI) hydrolysis was assayed in hippocampus from injured and sham-injured controls at 15 days following injury. At 15 days after central fluid percussion traumatic brain injury (TBI), the response to carbachol was enhanced by 30% and the response to trans-ACPD was enhanced by 75% compared to sham-injured animals. At 15 days after lateral fluid percussion TBI the response to trans-ACPD was enhanced by 40% both ipsilateral and contralateral to the side of injury. In contrast, the response to carbachol was enhanced by 29% contralateral to the side of injury but was diminished by 12% ipsilateral to the side of injury. Cresyl violet staining shows no hippocampal cell death after central fluid percussion injury or on the side contralateral to lateral fluid percussion injury but on the ipsilateral side cell death was identified in hippocampal area CA3. Thus, abnormal hippocampal cell signaling through the phosphoinositide pathway occurs in the absence of cell death and may contribute to cognitive impairment.

Animals↗

PubMed1995

Impaired gustatory neophobia following traumatic brain injury in rats.

To investigate the function of the amygdala following traumatic brain injury (TBI), rats were tested on a gustatory neophobia task that is sensitive to amygdala and hippocampal damage. Rats were either injured at a moderate level of fluid percussion injury (2.1 atm) or surgically prepared but not injured (sham-injury). Seven days after injury (n = 8) or sham injury (n = 9), rats were habituated to the testing chamber without food items present for 30 min. All rats were then food deprived. Twenty-four hours later, rats were placed in the testing chamber for 30 min and allowed to eat freely from four dishes of different foods: rat chow, raisins, potatoes, and cookies. Results showed that injured and sham-injured rats did not differ in their ability to find hidden food, suggesting that TBI does not produce an enduring impairment of olfaction. There was also no difference in the total amount of food eaten between injured and sham groups (p > 0.05). The percentage of each type of food consumed did differ between the two groups with sham controls consuming more familiar food (rat chow) compared to the unfamiliar foods (p < 0.01). The injured animals distributed their eating evenly among the four foods with no particular preference for any one food (p < 0.05). This pattern of eating behavior in injured animals is similar to animals that have lesions to both the hippocampus and amygdala (Sutherland and McDonald, 1990). Therefore, the results of this experiment suggest that, in addition to the hippocampus, the amygdala may also contribute to the behavioral changes observed following TBI.

Amygdala↗

PubMed1995

The effect of acute cocaine or lidocaine on behavioral function following fluid percussion brain injury in rats.

One of the goals of our laboratory is to examine how the presence of drugs of abuse will influence traumatic brain injury. Previous studies in our laboratory have shown that cocaine or lidocaine treatment before experimental fluid percussion brain injury in rats reduces the cortical hypoperfusion normally found in the early posttraumatic period. The purpose of the current study was to determine if pretreatment with cocaine or lidocaine is also associated with changes in trauma-induced suppression of reflexes and motor and cognitive dysfunction that occurs following traumatic brain injury (TBI). Twenty-four hours after surgical preparation, rats were randomly assigned to a saline or drug pretreatment group, cocaine (0.5, 2, or 5 mg/kg) or lidocaine (2 mg/kg), which was injected via the tail vein. None of the drug pretreatments worsened injury. Lidocaine and cocaine decreased the duration of suppression of some neurological reflexes and reduced posttraumatic body weight losses. Lidocaine and cocaine both decreased postinjury motor deficits. Lidocaine and cocaine did not affect cognitive function on days 11-15 postinjury. The mechanism by which lidocaine improves acute neurological and motor function following brain injury is unknown, but may involve improved posttraumatic cortical blood flow, as seen in our previous study. Our results, along with other studies showing lidocaine to be neuroprotective in animal models of ischemia, suggest that studies of the effect of posttraumatic administration of lidocaine are warranted.

Animals↗

PubMed1994

Traumatic brain injury causes a decrease in M2 muscarinic cholinergic receptor binding in the rat brain.

Numerous studies indicate that an acute, excessive activation of muscarinic acetylcholine receptors (mAChR) contributes to the pathophysiological sequela of TBI. The present study examined the effect of moderate fluid percussion traumatic brain injury (TBI) on binding to M1 and M2 mAChR subtypes in the hippocampal formation and adjacent cortex using quantitative autoradiography. Injured animals along with concurrent controls were sacrificed by in situ freezing at 3 h or 24 h following TBI. Slide-mounted tissue sections were incubated in either [3H]pirenzepine (23 nM) for M1 or [3H]AFDX384 (9 nM) for M2 mAChR subtype labeling. Binding of [3H]pirenzepine to the M1 mAChR subtype was not significantly altered by TBI when compared to sham-injured animals. [3H]AFDX384 binding to the M2 mAChR subtype was significantly decreased at 24 h in hippocampal CA2-3 region and dorsal blade of the dentate gyrus (P < 0.05). The differences observed between M1 and M2 subtypes suggests that these muscarinic subtypes may differentially contribute to the pathophysiology of TBI.

Animals↗

PubMed1994

Muscarinic cholinergic receptor binding in rat brain at 15 days following traumatic brain injury.

Laboratory studies indicate that activation of muscarinic cholinergic receptors (mAChRs) at or soon after traumatic brain injury (TBI) significantly contributes to behavioral morbidity. Recent research has demonstrated that pre-injury treatment with the muscarinic antagonist scopolamine significantly reduces spatial memory deficits at 11-15 days post-TBI. In the present study, we examined mAChR binding kinetics in brain regions at 15 days after moderate (1.95 atm) fluid percussion TBI in untreated and scopolamine-treated rats. Three groups were examined: untreated TBI (n = 8), TBI with pre-injury scopolamine treatment (1.0 mg/kg, i.p., 15 min prior to injury) (n = 11), and sham-injury (n = 7). The affinity (Kd) and maximum number of binding sites (Bmax) of mAChRs in hippocampus, neocortex, and brainstem were determined by [3H]QNB binding. Bmax values in TBI animals were significantly higher in hippocampus (4061 +/- 494 fmol/mg protein) and neocortex (4272 +/- 640 fmol/mg protein), but not in brainstem (833 +/- 39 fmol/mg protein) compared to sham-injured controls (hipp. 2812 +/- 218 fmol/mg/protein; neoctx. 2850 +/- 129 fmol/mg protein; brainstem 794 +/- 26 fmol/mg protein) (P < 0.05). At 15 days after injury, Bmax values of mAChRs in TBI animals with pre-injury scopolamine treatment (hipp. 2850 +/- 129 fmol/mg protein; neoctx. 2948 +/- 123 fmol/mg protein) did not differ from control. In all brain regions, Kd values did not differ between groups. These results demonstrate that TBI significantly alters the binding sites of mAChRs in hippocampus and neocortex for as long as 15 days after TBI. Furthermore, these results indicate that a pharmacological treatment that improves motor and memory function outcome also normalizes aspects of mAChRs physiology. These data suggest that excessive activation of mAChRs at or soon after TBI impact contributes to long-term pathophysiological processes in TBI.

Animals↗

PubMed1994

Muscarinic cholinergic receptor binding in rat brain following traumatic brain injury.

Recent evidence suggests that excessive activation of muscarinic cholinergic receptors (mAChRs) contributes significantly to the pathophysiological consequences of traumatic brain injury (TBI). To examine possible alterations in mAChRs after TBI, the affinity (Kd) and maximum number of binding sites (Bmax) of mAChRs in hippocampus, neocortex, brain stem and cerebellum were determined by [3H]QNB binding. Three groups of rats were examined: 1 h post-TBI (n = 21), 24 h post-TBI (n = 21) and sham-injured rats (n = 21). Kd values were significantly higher in hippocampus and brain stem at 1 but not 24 h post-TBI compared with sham-injured controls (P < 0.05). Kd values did not significantly differ in neocortex and cerebellum at 1 or 24 h post-TBI compared with sham-injured controls. Bmax values did not significantly differ in any brain areas at 1 or 24 h post-TBI compared with sham-injured controls. These results show that TBI significantly decreases the affinity of mAChRs in hippocampus and brain stem at an early stage post-TBI, which may contribute to desensitization of mAChRs after TBI. The findings of no change in Bmax values are consistent with a transient elevation in ACh concentrations after TBI.

Animals↗

PubMed1994

The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury.

The purpose of the present experiment was to examine the effectiveness of a modified rotarod test in detecting motor deficits following mild and moderate central fluid percussion brain injury. In addition, this investigation compared the performance of the rotarod task with two other commonly used measures of motor function after brain injury (beam-balance and beam-walking latencies). Rats were either injured with a mild (n = 14) or moderate (n = 8) level of fluid percussion injury or were surgically prepared but not injured (n = 8). All rats were assessed on all tasks for 5 days following their respective treatments. Results revealed that both the mild and moderate injury levels produced significant deficits in the ability of the animals to perform the rotarod task. Performance on the beam-balance and beam-walking tasks were not significantly impaired at the mild injury level. It was only at the moderate injury level that the beam-balance and beam-walking tasks detected deficits in motor performance. This result demonstrated that the rotarod task was a sensitive index of injury-induced motor dysfunction following even mild fluid percussion injury. A power analysis of the three tasks indicated that statistically significant group differences could be obtained with the rotarod task with much smaller sample sizes than with the beam-balance and beam-walking tasks. Performance on the rotarod, beam-walk, and beam-balance tasks were compared and evaluated by a multivariate stepdown analysis (multiple analysis of variance followed by univariate analyses of covariance). This analysis indicated that the rotarod task measures aspects of motor impairment that are not assessed by either the beam-balance or beam-walking latency. These findings suggest that compared to the beam-balance and beam-walking tasks, the rotarod task is a more sensitive and efficient index for assessing motor impairment produced by brain injury.

Animals↗

PubMed1994

Combined fluid percussion brain injury and entorhinal cortical lesion: a model for assessing the interaction between neuroexcitation and deafferentation.

Laboratory studies suggest that excessive neuroexcitation and deafferentation contribute to long-term morbidity following human head injury. Because no current animal model of traumatic brain injury (TBI) has been shown to combine excessive neuroexcitation and significant levels of deafferentation, we developed a rat model combining the neuroexcitation of fluid percussion TBI with subsequent entorhinal cortical (EC) deafferentation. In this paradigm, moderate fluid percussion TBI was induced in each rat, followed 24 h later by bilateral EC lesion (BEC). Six conditions were examined: (1) fluid percussion TBI followed 24 h later by bilateral EC lesion (TBEC), (2) fluid percussion TBI (TBI), (3) bilateral EC lesion (BEC), (4) sham fluid percussion TBI (SHAM), (5) TBI followed 24 h later by unilateral EC lesion (TUEC), and (6) unilateral EC lesion (UEC). The first four groups were assessed for motor (with beam-balance and beam-walk testing) and cognitive deficits (with the Morris water maze) and hippocampal morphology (with immunocytochemistry and electron microscopy). The TUEC and UEC groups were assessed for cognitive deficits alone. Motor deficits were greater in the TBEC injury than in TBI or sham alone; however, no significant difference was observed between the TBEC and BEC conditions in motor performance. Cognitive deficits were of a greater magnitude in the combined TBEC injury model relative to each individual insult. These cognitive deficits appeared to be additive for the two experimental injuries, BEC deafferentation producing deficits intermediate between TBI and TBEC insults. Morphologic analysis of the dentate gyrus molecular layer at 15 days after TBEC showed that the distribution of synaptophysin-positive presynaptic terminals was distinct from that observed after either TBI or BEC alone. Specifically, the laminar pattern of presynaptic rearrangement induced by BEC lesion did not occur after TBEC injury. The present results show that axonal injury and its attendant deafferentation, when coupled with traumatically induced neuroexcitation, produce an enhancement of the morbidity associated with TBI. Moreover, they indicate that this model can effectively be used to study the interaction between neuroexcitation and synaptic plasticity.

Animals↗

PubMed1994

Protective effect of galanin on behavioral deficits in experimental traumatic brain injury.

The magnitude of behavioral deficits in traumatic brain injury (TBI) has been shown to be partly related to alterations in the balance between excitatory and inhibitory neurotransmitter release. Previous studies have demonstrated that extracellular excitatory neurotransmitter concentrations dramatically increase following experimental TBI. We examined the effects of a neuromodulatory peptide, galanin (GAL), on behavioral morbidity, as measured by sensory motor and memory performance tasks, associated with experimental TBI in the rat. A single intraventricular injection of GAL (1.0 micrograms, n = 8 or 10.0 micrograms, n = 10) or cerebrospinal fluid (CSF) vehicle (n = 10) was administered 5 minutes prior to central fluid percussion TBI in rats. Performance on sensory motor tasks was assessed prior to injury and for 5 days after TBI with beam-balance, beam-walking, and rotarod tasks. Memory performance was assessed on days 11-15 after TBI with the Morris water maze. TBI produced significant motor and memory deficits in the CSF-treated group. GAL-treated rats had significantly less magnitude of deficits compared to CSF-treated rats on beam-balance, beam-walking, and rotarod performance. The 1.0 micrograms GAL dose produced slightly greater protection than the 10.0 micrograms GAL dose. Neither GAL dose affected body weight loss or Morris water maze performance. These results suggest that the physiologic effects of GAL may reduce certain components of TBI morbidity, possibly by modulating neuronal excitability.

Animals↗

PubMed1994

Traumatic brain injury enhances the amnesic effect of an NMDA antagonist in rats.

The authors have examined the effect of experimental traumatic brain injury on the amnesia produced by the N-methyl-D-aspartate (NMDA) antagonist MK-801. Rats were either subjected to a moderate level of fluid-percussion injury or prepared for injury but not injured ("sham injury"). Nine days following injury or sham injury, the rats were injected either with saline (sham/saline group, nine rats; injured/saline group, nine rats) or with 0.1 mg/kg of MK-801 (sham/MK-801 group, nine rats; injured/MK-801 group, eight rats) 30 minutes before being trained on a passive-avoidance task. Twenty-four hours later, the rats were tested for retention of the passive-avoidance task. Results revealed that the low dose of MK-801 did not significantly affect retention of the passive-avoidance task in the sham-injured group. In injured animals, administration of MK-801 produced a profound amnesia in contrast to the sham-injured animals treated with MK-801 and the injured animals treated with saline. To further investigate this enhanced sensitivity to the amnesic effects of MK-801 exhibited by the injured animals, nine injured and eight sham-injured rats were injected with 0.3 mg/kg of MK-801 15 minutes before injury. Results indicated that the animals treated with MK-801 before injury did not significantly differ from the sham-injured animals in retention of the passive-avoidance task. In addition, test results in the animals treated with MK-801 before injury and reinjected with MK-801 before passive-avoidance testing did not differ from those in untreated injured animals reinjected with saline before passive-avoidance testing. These findings indicate that MK-801 treatment before injury prevented the enhanced sensitivity to MK-801-induced amnesia that follows traumatic brain injury.

Amnesia↗

PubMed1993

Selective cognitive impairment following traumatic brain injury in rats.

Impairment of cognitive abilities is a frequent and significant sequelae of traumatic brain injury (TBI). The purpose of this experiment was to examine the generality of the cognitive deficits observed after TBI. The performance of three tasks was evaluated. Two of the tasks (passive avoidance and a constant-start version of the Morris water maze) were chosen because they do not depend on hippocampal processing. The third task examined was the standard version of the Morris water maze which is known to rely on hippocampal processing. Rats were either injured at a moderate level (2.1 atm) of fluid percussion brain injury or surgically prepared but not injured (sham-injured control group). Nine days after fluid percussion injury, injured (n = 9) and sham-injured rats (n = 8) were trained on the one-trial passive avoidance task with retention assessed 24 h later. On days 11-15 following injury, injured (n = 9) and sham-injured (n = 8) rats were trained on a constant-start version of the Morris water maze that has the animals begin the maze from a fixed start position on each trial. Additional injured (n = 8) and sham-injured (n = 8) animals were trained on days 11-15 after injury on the standard (i.e. using variable start positions) version of the Morris water maze. The results of this experiment revealed that performance of the passive avoidance and the constant-start version of the Morris water maze were not impaired by fluid percussion TBI.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Combined scopolamine and morphine treatment of traumatic brain injury in the rat.

Previous studies have indicated that either scopolamine (1.0 mg/kg) or morphine (10.0 mg/kg) administered to rats prior to or soon after moderate fluid percussion traumatic brain injury (TBI) reduces behavioral deficits associated with injury. In this study, a series of experiments examined the effects of a combination of these drugs, as well as each drug individually, on behavioral outcome, brain temperature, and systemic physiological responses to TBI. Experiment I: a single systemic bolus injection of scopolamine (n = 10), morphine (n = 11), scopolamine plus morphine (n = 11), or saline (n = 10) was administered to rats 15 min prior to TBI. Animals were assessed on beam-walking behavioral performance for 5 days after injury. Scopolamine alone or morphine alone significantly reduced (P < 0.05) deficits produced by injury. Treatment with a combination of scopolamine and morphine provided greater protection on beam-walking behavioral measures than either drug alone. Experiment II: morphine raised brain temperature in uninjured rats (n = 5) to a mean of 39.3 degrees C +/- 0.3 by 60 min post-injection. Neither scopolamine (n = 5) nor scopolamine plus morphine (n = 5) altered brain temperature. Experiment III: scopolamine (n = 7) significantly raised heart rate for 5 min after injury. Saline (n = 8), morphine (n = 9) and scopolamine plus morphine (n = 7) significantly lowered heart rate after injury. All four groups had similar hypertensive responses to TBI which peaked at 10 s after injury. The results confirm that pharmacological blockade of muscarinic receptors or stimulation of mu opioid receptors reduces functional deficits associated with TBI.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗