Biomedical subjects

T K McIntosh

Publications and source records attributed to T K McIntosh.

At least 145 records · Page 8Linked to original sources

PubMed1993

Activation of kappa-opioid receptors in the nucleus ambiguus does not affect cardiovascular function or outcome following acute hemorrhage in the rat.

The central cardiovascular response to hemorrhage is believed to be regulated, in part, by specific brain cardioregulatory nuclei, including the nucleus ambiguus (NA) of the hindbrain. Since endogenous opioid peptides and opiate receptors have been localized to this brain region, activation of endogenous opioid systems in the NA may affect the cardiovascular response to acute hemorrhage. The present study examined the effects of intracerebral microinjection of kappa-receptor agonists into the NA prior to acute fixed-volume hemorrhage in awake rats. 15 min prior to fixed volume hemorrhage (7.5 ml/300 g), male Sprague-Dawley rats (n = 59) received a microinjection of either (1) the synthetic kappa-receptor agonist U-50,488H (10 nM) or (2) U-50,488H (100 nM) or (3) the endogenous kappa-receptor agonist dynorphin 1-17 (1 nM) or (4) Des-Tyr dynorphin 2-17, inactive at opiate receptors (1 nM) or (5) equal volume saline. With the exception of the first 10 min post-hemorrhage, where intracerebral injection of both dynorphin 1-17 and dynorphin 2-17 caused a transient suppression of mean arterial blood pressure (P < 0.05 when compared to saline-treated controls), microinjection of the kappa-agonists dynorphin 1-17 or U-50,488H had no effect on blood pressure, heart rate or mortality when compared to control animals. These results suggest that activation of kappa-opiate receptors in the NA does not markedly influence cardiovascular response to acute hemorrhage.

Animals↗

PubMed1993

Antagonists of excitatory amino acids and endogenous opioid peptides in the treatment of experimental central nervous system injury.

Trauma to the central nervous system can lead to primary injuries occurring at the time of impact as well as secondary or delayed injury processes that can result from cellular hypoxia, oligemia/ischemia, edema and swelling, and intracranial hypertension that are manifested over a period of hours to weeks after the initial event. Although the mechanisms underlying delayed tissue injury are poorly understood, they appear to be associated with endogenous neurochemical changes resulting from traumatic nervous system injury. These neurochemical changes may include excessive neurotransmitter release, deregulation of ion homeostasis, and the synthesis, release, or activation of various "autodestructive" neurochemical factors. Experimental studies over the past decade indicate that these alterations mediate important components of the neurochemical cascade leading to central nervous system injury. Furthermore, pharmacologic manipulations of these neurochemical changes have been reported to attenuate secondary central nervous system damage, ameliorate neuronal death, and promote functional recovery after central nervous system injury. This article focuses on the role of excitatory amino acid neurotransmitters, endogenous opioid peptides, and magnesium in the pathophysiology of central nervous system injury and on the therapeutic manipulation of these systems to improve functional outcome after central nervous system injury.

Amino Acids↗

PubMed1993

Novel pharmacologic therapies in the treatment of experimental traumatic brain injury: a review.

Delayed or secondary neuronal damage following traumatic injury to the central nervous system (CNS) may result from pathologic changes in the brain's endogenous neurochemical systems. Although the precise mechanisms mediating secondary damage are poorly understood, posttraumatic neurochemical changes may include overactivation of neurotransmitter release or re-uptake, changes in presynaptic or postsynaptic receptor binding, or the pathologic release or synthesis of endogenous "autodestructive" factors. The identification and characterization of these factors and the timing of the neurochemical cascade after CNS injury provides a window of opportunity for treatment with pharmacologic agents that modify synthesis, release, receptor binding, or physiologic activity with subsequent attenuation of neuronal damage and improvement in outcome. Over the past decade, a number of studies have suggested that modification of postinjury events through pharmacologic intervention can promote functional recovery in both a variety of animal models and clinical CNS injury. This article summarizes recent work suggesting that pharmacologic manipulation of endogenous systems by such diverse pharmacologic agents as anticholinergics, excitatory amino acid antagonists, endogenous opioid antagonists, catecholamines, serotonin antagonists, modulators of arachidonic acid, antioxidants and free radical scavengers, steroid and lipid peroxidation inhibitors, platelet activating factor antagonists, anion exchange inhibitors, magnesium, gangliosides, and calcium channel antagonists may improve functional outcome after brain injury.

Animals↗

PubMed1993

Beneficial effect of the nonselective opiate antagonist naloxone hydrochloride and the thyrotropin-releasing hormone (TRH) analog YM-14673 on long-term neurobehavioral outcome following experimental brain injury in the rat.

Neurobehavioral dysfunction following traumatic brain injury results, in part, from delayed biochemical changes initiated by the traumatic insult. Endogenous opioid peptides have been implicated as one type of neurochemical factor involved in the delayed pathological sequelae of central nervous system (CNS) injury, including brain trauma. Both opiate antagonists and thyrotropin-releasing hormone (TRH) and its analogs, which antagonize the physiologic effects of endogenous opioids, have been shown to improve cardiovascular, cerebrovascular, metabolic, and neurologic status following both traumatic and ischemic CNS injury. The present study evaluated the ability of the opiate antagonist naloxone hydrochloride to improve posttraumatic neurologic motor function following experimental fluid-percussion brain injury in the rat, and compared the therapeutic effectiveness of naloxone to the long-acting, centrally active TRH analog YM-14673. Thirty minutes following fluid-percussion brain injury of moderate severity, animals received an intravenous bolus of either naloxone (2.0 mg/kg with constant infusion of 1.7 mg/kg/h, n = 8), YM-14673 (1.0 mg/kg, n = 8), or saline (n = 8). Although naloxone caused a modest and nonsignificant increase in mean arterial blood pressure (MAP); YM-14673 significantly increased MAP within 5 min of administration (p < 0.05), an effect that continued up to 4 h postinjury. Postinjury administration of both naloxone and YM-14673 caused a significant improvement in neurobehavioral outcome which persisted up to 4 weeks postinjury. These results suggest that endogenous opioid peptides may be involved in the pathologic response to traumatic CNS injury and that pharmacotherapies directed at antagonizing opioid peptides may enhance neurobehavioral recovery after brain injury.

Animals↗

PubMed1993

Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus.

Memory dysfunction following mild human traumatic brain injury (TBI) is a common clinical observation, but the pathologic substrate underlying this loss of function has not been well-characterized. In the present study, we examined the effects of a mild lateral fluid percussion (FP) brain injury on memory dysfunction, neuronal cell loss in specific regions of the hippocampus, and breakdown of the blood-brain barrier (BBB). A Morris Water Maze (MWM) memory paradigm was used to assess memory retention in rats 42 h after lateral FP brain injury (n = 11) or sham injury (n = 10). At the completion of cognitive testing, animals were sacrificed and neuronal cell loss in the hippocampi was examined with Nissl staining. Immunoreactivity to anti-rat IgG was used to evaluate the extent of BBB disruption. A significant correlation was observed between posttraumatic memory scores and neuronal loss in the hilus of the dentate gyrus (p < 0.005). To our knowledge, these observations are the first to suggest an association between cognitive deficits following a mild experimental brain injury and neuropathological changes in the hippocampus.

Animals↗

PubMed1993

Measurement of hippocampal levels of cellular second messengers following in situ freezing.

The in situ freezing technique has been widely used to fix labile metabolites and cellular second messengers in cerebral cortex. In this study, we isolated specific brain regions at 0 degree C from coronal sections of frozen heads following in situ brain freezing and measured regional concentrations of labile metabolites and cellular messengers. These levels in the cortex were compared with those in cortical punches obtained at freezing temperature (less than -40 degrees C) from the same in situ frozen brains and those of cortex dissected from decapitated animals. In both isoflurane- and pentobarbital-anesthetized animals, we observed that the levels of lactate, free fatty acids, inositol 1,4,5-trisphosphate, and diacylglycerol, as well as the proportion of protein kinase C associated with the membrane fraction, were similar in cortical punches taken at freezing temperature and those dissected at 0 degree C. However, with animals decapitated at room temperature, cortical and hippocampal levels of lactate, free fatty acids, and inositol 1,4,5-trisphosphate and the proportion of membrane protein kinase C were significantly higher than those of corresponding brain regions isolated at 0 degree C from in situ frozen brains (p < 0.05). These results indicate that dissection of cortex and hippocampus at 0 degree C following in situ freezing will eliminate decapitation-induced production of artifacts and changes in the levels of cellular second messengers such as inositol 1,4,5-trisphosphate, diacylglycerol, and protein kinase C. The present technique, used in conjunction with in situ freezing, will fix cellular second messengers and labile metabolites in several regions of brain and may facilitate accurate characterization of molecular and cellular mechanisms underlying CNS function.

Animals↗

PubMed1993

Effect of dynorphin microinjection in the anterior hypothalamus (AV3V) region on the hemodynamic response to hemorrhage in the rat.

The region surrounding the anteroventral part of the third ventricle (AV3V) is important for the regulation of cardiovascular homeostasis. In the present study we investigated the effect of the kappa-opioid receptor agonists dynorphin A-(1-17) and dynorphin A-(1-13) microinjected into the AV3V region on mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and left ventricular stroke work (LVSW) during fixed-volume hemorrhage in conscious rats. During fixed-volume hemorrhage (8 ml/300 g), dynorphin A-(1-17) (6 nmol), microinjected into the AV3V, significantly decreased MAP up to 30 min postinjection (P < 0.05). Recovery of MAP, SV, and LVSW in the dynorphin A-(1-17) group following hemorrhage was found to be significantly attenuated compared to that in animals receiving microinjection of normal saline (NS) vehicle into the AV3V (P < 0.05). Hypothalamic microinjection of dynorphin A-(1-13) (6 nmol) also attenuated the recovery of SV following hemorrhage compared with the NS group (P < 0.05). No significant effects were observed on HR or CO following microinjection of dynorphin into the AV3V region. The results of this study suggest that activation of the kappa-opiate receptor system in the AV3V region of the hypothalamus can attenuate the compensatory cardiovascular responses to hemorrhage.

Animals↗

PubMed1993

Effects of the excitatory amino acid receptor antagonists kynurenate and indole-2-carboxylic acid on behavioral and neurochemical outcome following experimental brain injury.

The overactivation of the NMDA receptor is thought to be a major contributor to the pathophysiologic sequelae of traumatic brain injury (TBI), which commonly includes memory dysfunction. Uniquely, potentiation of the NMDA receptor is dependent on the binding of glycine to a distinct site on the receptor. Despite the potential role of the NMDA receptor in the development of post-TBI cognitive deficits, no studies to date have evaluated the efficacy of NMDA receptor antagonists on memory dysfunction after brain injury. Moreover, glycine site antagonists have not been employed as potential therapeutic agents in models of TBI. In the present study, we evaluated the effects of two glycine site antagonists, kynurenate (KYNA) and indole-2-carboxylic acid (I2CA), on memory and motor dysfunction, cerebral edema formation, and changes in regional total tissue brain [Na], [K], [Ca], [Mg], and [Zn], following lateral fluid-percussion brain injury in the rat. We found that both KYNA (300 mg/kg) and I2CA (50 mg/kg and 20 mg/kg) administered 15 min postinjury dramatically attenuated trauma-induced cognitive dysfunction (p < 0.01). In addition, both compounds improved neurologic motor deficits measured at 2 weeks following injury (p < 0.05). KYNA (300 mg/kg) reduced edema in the cortex, hippocampus, and thalamus, while I2CA (20 mg/kg) reduced edema formation only in the thalamus. Differential effects of KYNA and I2CA on cation concentrations were also noted. KYNA attenuated the postinjury increase in regional tissue [Ca]; however, it had little effect on other cation concentrations. I2CA reversed the postinjury regional increases in [Na] and decreases in [K], [Mg], and [Zn], but had little effect on [Ca] changes. These results indicate that KYNA and I2CA may have differential, but beneficial effects on both behavioral and neurochemical sequelae of TBI.

Animals↗

PubMed1993

Alteration in regional brain catecholamines during and after acute hemorrhage in the rat.

Using high-performance liquid chromatography (HPLC), we carried out a simultaneous assay of norepinephrine (NE), epinephrine (E), and dopamine (DA) in specific brain regions before and at 5 min, 30 min, 1 hr, 2 hr, and 24 hr following acute hemorrhage in the rat. Thirty-six awake male Sprague-Dawley rats were subjected to rapid fixed-volume hemorrhage (8.5 ml/300 g) over 5 min. In the hypothalamus, concentrations of NE and E fell markedly and significantly by 5 min posthemorrhage (P < 0.001), while hypothalamic DA concentrations fell gradually to reach a nadir by 2 hr (P < 0.005). Hypothalamic concentrations of all three catecholamines remained significantly reduced up to 24 hr posthemorrhage. Dopamine concentrations in the medulla increased transiently, while striatal DA concentrations fell following hemorrhage to reach a nadir by 2 hr (P < 0.001). By 2 hr posthemorrhage, NE concentrations in both cortex and medulla were significantly decreased (P < 0.01 and P < 0.005, respectively), with cortical NE levels remaining significantly depressed for up to 24 hr. These results suggest that regional and prolonged changes occur in central catecholaminergic systems following acute, uncompensated hemorrhage. It is possible that these changes in the central nervous system contribute to the cardiovascular dysfunction observed following hemorrhage.

Acute Disease↗

PubMed1993

Regulation of the gene expression of preproenkephalin in the rat brain: influence of hemorrhage.

In the present study, we examined the expression of the gene encoding for the production of the opioid peptide enkephalin in specific brain regions during hemorrhage in the conscious rat. Rats were subjected to fixed-volume (8 ml/300 g) bleeding via jugular vein within 10 min. Total RNA was isolated from rat brain tissue using the hot phenol/chloroform method. Preproenkephalin transcript levels were quantified using Northern blot hybridization of total RNA with alpha-32P-labeled cDNA probe, and autoradiograms were scanned with a densitometer. The ppENK transcript in midbrain was significantly elevated following one and two hours of hemorrhage compared to control group (P < 0.01). The ppENK transcript in spinal cord was also significantly increased after two hours of hemorrhage, when compared with control group (P < 0.01). In the brainstem, ppENK transcript was significantly decreased after both 1 and 2 hr of hemorrhage compared with control values (P < 0.01). These results indicate that hemorrhage acutely changes levels of the transcript of ppENK in specific brain regions. It is possible that the changes in brainstem ppENK transcript may be a mechanism by which certain inhibitory effects of enkephalins on important brain cardiovascular regulatory centers are mediated.

Animals↗

PubMed1992

Changes in neuropeptide Y after experimental traumatic brain injury in the rat.

We utilized a model of fluid percussion (FP) brain injury in the rat to examine the hypothesis that alterations in brain neuropeptide Y (NPY) concentrations occur following brain injury. Male rats (n = 44) were subjected to FP traumatic brain injury. One group of animals (n = 38) was killed at 1 min, 15 min, 1 h, or 24 h after brain injury, and regional brain homogenates were analyzed for NPY concentrations using radioimmunoassay. A second group of animals (n = 6) was killed for NPY immunocytochemistry. Concentrations of NPY in the injured left parietal cortex were significantly elevated at 15 min post injury (p less than 0.05). No changes were observed in other brain regions. NPY-immunoreactive fibers were seen at 15 min post injury predominantly in the injured cortex and adjacent hippocampus. These temporal changes in NPY immunoreactivity, together with previous observations concerning posttraumatic changes in regional CBF in these same areas, suggest that an increase in region NPY concentrations after brain injury may be involved in part in the pathogenesis of posttraumatic hypoperfusion.

Animals↗

PubMed1992

Decreased alpha 1-adrenergic receptors after experimental brain injury.

The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, to alterations in the balance between excitatory and inhibitory neurotransmitters. Previous studies have implicated a role of central inhibitory noradrenergic mechanisms in the pathophysiologic sequelae of traumatic brain injury. In the present study, we examined alpha 1-adrenergic receptor binding after parasaggital lateral fluid percussion (FP) brain injury of moderate severity (2.3 atm) in the rat. At 30 min following injury, the specific binding of [3H]prazosin to membranes isolated from left cortex (injury site) was reduced by 37% in brain-injured animals when compared to sham-operated noninjured animals (p < 0.05). However, there were no significant differences in [3H]prazosin binding to membranes of either contralateral (right) cortex or left and right hippocampi between brain-injured and sham-operated animals. Conversely, at 24 h posttrauma, specific binding to membranes of left cortex, cortex adjacent to injury site, contralateral (right) cortex, and left hippocampus was reduced by 25%, 16%, 27%, and 24%, respectively (all p < 0.05). Scatchard analysis revealed that a reduction of [3H]prazosin binding to membranes of injured animals resulted from a decrease in alpha 1-receptor binding density (B-max) but not from changes in ligand affinity. Histopathologic assessment of neuronal damage at 24 h postinjury revealed neuronal loss within injury site cortex and left hippocampus but no clearly discernible cell loss in contralateral right cortex, suggesting that the decrease in B-max might be a consequence of early pathophysiology of trauma rather than of neuronal cell loss. We suggest that alterations in alpha 1-adrenergic receptors after brain injury may result in decreased inhibitory neurotransmitter action of norepinephrine and may thus contribute to the pathophysiology of traumatic brain injury.

Animals↗

PubMed1992

The novel 21-aminosteroid U74006F attenuates cerebral edema and improves survival after brain injury in the rat.

The present study evaluated the effect of the nonglucocorticoid 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on the development of regional cerebral edema after lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (n = 40) were anesthetized and subjected to FP brain injury of moderate severity centered over the left parietal cortex (2.5-2.6 atms). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 21) followed by a second bolus (3 mg/kg) at 3 hr or buffered sodium citrate vehicle (equal volume, n = 15). An additional group of 12 surgically prepared but uninjured animals served as preinjury controls. At 48 hr after injury, animals were sacrificed and brain tissue assayed for water content and regional cation concentrations. With the use of specific gravimetric techniques, no significant differences were observed in posttraumatic cerebral edema between drug- and control-treated animals. However, using wet weight/dry weight methodology, we found that administration of U74006F significantly reduced water content in the right hippocampus (contralateral to the site of injury) compared to saline-treated animals (p less than 0.05). U74006F also significantly prevented the postinjury increase in sodium concentrations in the ipsilateral hippocampus (p less than 0.05) and thalamus (p less than 0.03). Regional concentrations of potassium were unaltered after drug treatment. Administration of U74006F significantly reduced postinjury mortality, from 28% in control animals to zero in treated animals (p = 0.01). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21-aminosteroids may be beneficial in the treatment of brain injury.

Animals↗

PubMed1992

Development of prolonged focal cerebral edema and regional cation changes following experimental brain injury in the rat.

The present study examined the formation of regional cerebral edema in adult rats subjected to lateral (parasagittal) experimental fluid-percussion brain injury. Animals receiving fluid-percussion brain injury of moderate severity over the left parietal cortex were assayed for brain water content at 6 h, 24 h, and 2, 3, 5, and 7 days post injury. Regional sodium and potassium concentrations were measured in a separate group of animals at 10 min, 1 h, 6 h, and 24 h following fluid-percussion injury. Injured parietal cortex demonstrated significant edema, beginning at 6 h post injury (p less than 0.05) and persisting up to 5 days post injury. In the hippocampus ipsilateral to the site of cortical injury, significant edema occurred as early as 1 h post injury (p less than 0.05), with resolution of water accumulation beginning at 3 days. Sodium concentrations significantly increased in both injured cortex (1 h post injury, p less than 0.05) and injured hippocampus (10 min post injury, p less than 0.05). Potassium concentrations fell significantly 1 h post injury within the injured cortex (p less than 0.05), whereas significant decreases were not observed until 24 h post injury within the injured hippocampus. Cation alterations persisted throughout the 24-h post injury period. These results demonstrate that regional brain edema and cation deregulation occur in rats subjected to lateral fluid-percussion brain injury and that these changes may persist for a prolonged period after brain injury.

Animals↗

PubMed1992

Evaluation of a novel calcium channel blocker, (S)-emopamil, on regional cerebral edema and neurobehavioral function after experimental brain injury.

The authors investigated the effects of a novel calcium channel blocker, (S)-emopamil, on cerebral edema and neurobehavioral and memory function following experimental fluid-percussion brain injury in the rat. Two independent experiments were performed to evaluate the effects of this compound on cardiovascular variables and postinjury cerebral edema (increases in tissue water content), and on cognitive deficits and neurological motor function following brain injury. Treatment with (S)-emopamil significantly reduced focal brain edema at 48 hours after brain injury. Profound memory dysfunction induced by brain injury was significantly attenuated following (S)-emopamil treatment. In addition, (S)-emopamil also attenuated the deficits in motor function that were observed over a 2-week period following brain injury. These results suggest that changes in calcium homeostasis may play an important role in the pathogenesis of trauma to the central nervous system and that the calcium channel blocker (S)-emopamil might be a useful compound for the treatment of traumatic brain injury.

Animals↗

PubMed1992

Selective vulnerability of dentate hilar neurons following traumatic brain injury: a potential mechanistic link between head trauma and disorders of the hippocampus.

Despite intensive study, the neurobiological basis of epilepsy and persistent memory impairment following traumatic head injury remains unknown. Since abnormalities of the hippocampus are known to be associated with temporal lobe seizures and memory dysfunction, we investigated the effects of experimental traumatic brain injury on hippocampal structure and function in the rat. Using a model of fluid-percussion injury, we have discovered that neurons of the dentate hilus are vulnerable to a brief, unilateral impact to the extradural surface of the brain. One week after trauma, there was a dramatic reduction in hilar neurons ipsilateral to the impact, and a milder but significant decrease in neurons on the contralateral side as well. This neuronal loss was highly selective since adjacent dentate granule and pyramidal neurons appeared relatively unaffected. Immunocytochemistry showed that the hilar cell loss included a loss of somatostatin-immunoreactive neurons, and degeneration stains provided evidence that irreversible hilar injury occurred within 4 hr of impact. To assess the functional effects of the hilar damage, dentate granule cell field potentials were measured in response to perforant path stimulation. This revealed abnormal dentate granule cell hyperexcitability at 2.0 Hz stimulation in many of the injured animals. The presence of abnormal hyperexcitability correlated with the loss of hilar neurons. Thus, a momentary impact to the surface of the brain can cause selective, bilateral hippocampal injury with associated abnormalities in dentate gyrus physiology. Furthermore, the pattern of cell loss is similar to that observed in some patients with temporal lobe epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Pharmacologic strategies in the treatment of experimental brain injury.

Although the mechanisms underlying secondary or delayed damage after traumatic injury to the central nervous system (CNS) are poorly understood, delayed neuronal injury may result from pathologic changes in the brain's endogenous neurochemistry. These neurochemical changes may include the overactivation of neurotransmitter release systems, changes in presynaptic or postsynaptic receptor binding, or the pathologic release or synthesis of autodestructive injury factors. Identification of such factors and the timing of the neurochemical cascade after CNS injury provides a window of opportunity for treatment with pharmacologic agents that modify synthesis, release, receptor binding, or physiologic activity with subsequent limitation of damage and disability. Over the past decade, a number of experimental studies have reported that modification of postinjury events by pharmacologic manipulation can promote functional recovery in a variety of animal models of CNS injury. This article summarizes the recent work suggesting that endogenous opioid peptides, catecholamines, and magnesium all play a role in the pathophysiologic cascade after brain injury and that pharmacologic manipulation of these endogenous systems may improve functional outcome after brain injury.

Animals↗

PubMed1991

Alterations in regional cerebral blood flow following brain injury in the rat.

To elucidate the temporal changes in regional cerebral blood flow (rCBF) after experimental traumatic brain injury, serial rCBF measurements were made during a 24-h period following fluid-percussion (F-P) traumatic brain injury in the rat. Brain injury of 2.2 atm was induced over the left parietal cortex and serial measurements of rCBF were performed using the radiolabeled microsphere method. rCBF values were obtained prior to injury and at 15 and 30 min and 1, 2, 4, and 24 h postinjury. At 15 min postinjury, there was a profound, wide-spread reduction in rCBF in all brain regions studied (p less than 0.05). At 30 min and 1 h postinjury, all brain regions except pons-medulla and cerebellum showed significantly reduced rCBF compared to the preinjury values (p less than 0.05). By 2 h postinjury, however, a significant focal reduction of rCBF was observed only in the cerebral tissue surrounding the trauma site (p less than 0.05); rCBF in the remaining brain regions had recovered to the preinjury levels. By 4 h postinjury, rCBF had returned to normal in all brain regions studied. This recovery of rCBF was still evident at 24 h postinjury. The present study demonstrates that, following the experimental traumatic brain injury in the rat, (a) an initial global suppression of rCBF occurs up to 1 h postinjury; (b) at the trauma site, a more persistent focal reduction of rCBF occurs; and (c) these alterations in rCBF after trauma dissolve by 4 h postinjury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗