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Biomedical subjects

R L Hayes

Publications and source records attributed to R L Hayes.

At least 127 records · Page 7Linked to original sources
PubMed1990

Excitatory amino acid receptor subtype binding following traumatic brain injury.

Sprague-Dawley rats were subjected to a moderate level (2.2 atm) of traumatic brain injury (TBI) using fluid percussion. Injured animals were allowed post-trauma survival periods of 5 min, 3 and 24 h. Regional glutamate receptor subtype binding was assessed with quantitative autoradiography in each group for N-methyl-D-aspartate (NMDA), quisqualate and kainate receptor subpopulations at approximately the -3.8 bregma level and compared to a sham control group. [3H]glutamate binding to the NMDA receptor was significantly (P less than 0.05) decreased at 3 h post-TBI in the hippocampal CA1 stratum radiatum, the molecular layers of the dentate gyri and the outer (layers 1-3) and inner (layers 5 and 6) overlying neocortex. NMDA receptor binding was significantly reduced in layers 5 and 6 of the neocortex at all post-trauma survival times but no further differences were seen in the hippocampi. No significant changes were observed with [3H]AMPA binding to quisqualate receptors and [3H]KA binding was significantly reduced only in layers 5 and 6 of the neocortex at 24 h after TBI. These data further confirm the pathological involvement of the NMDA receptor complex in brain regions selectively vulnerable to moderate levels of TBI in this model.

Animals↗
PubMed1990

Effect of experimental subarachnoid hemorrhage on CSF eicosanoids in the rat.

A simple and inexpensive experimental model of subarachnoid hemorrhage (SAH) was developed in the rat. Based on accumulating data indicating the important role of arachidonic acid metabolites in the etiology of delayed cerebral vasospasm, we investigated changes induced by SAH on cerebrospinal fluid (CSF) levels of prostaglandin E2 (PGE2), F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2). SAH was produced by the cisternal injection of blood via percutaneous suboccipital puncture. SAH rats (n = 200) were injected with 300 microliters of fresh autologous arterial blood; Control rats (n = 100) received the same volume of mock CSF. In 60 additional animals, no injections were made. To follow the changes induced by SAH on both the spectrum and time course of CSF eicosanoids, cisternal CSF samples were collected under basal conditions, 6, 12, and 36 after cisternal injection. PGE2, PGF2 alpha, and TXB2 were assayed in aliquots of CSF obtained by pooling samples from each experimental group. Eicosanoids were assayed using radioimmunoassay techniques. Arterial spasm was verified in parallel groups of SAH and control rats by comparison of the angiographic diameters of the basilar arteries (BA) and middle cerebral arteries (MCA) to that of the stapedial artery. CSF levels of all three eicosanoids were significantly higher in the SAH groups compared to both noninjected and mock-CSF injected control rats. These increases in concentrations of eicosanoids were accompanied by a decrease in the mean vascular diameter (77.5-82.0% of control) on day 2 following cisternal injection. We conclude that marked elevations of spasmogenic eicosanoids in the CSF are associated with experimental SAH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Beta-endorphin in cerebrospinal fluid and serum after severe head injury.

Endogenous opioids have been implicated as a cause of secondary damage after neural injury. The basis for this statement is primarily indirect evidence from studies that demonstrate neurological or physiological improvement when opiate antagonists are given. This study directly evaluates the level of the endogenous opioid beta-endorphin in 15 patients with severe head injury. Levels of immunoreactive beta-endorphin (ir-beta E) from ventricular cerebrospinal fluid (vCSF) and serum were determined less than 24 hours after trauma. No significant correlation was found with the degree of initial injury, age, sex, or either 6- or 12-month outcome. Levels of ir-beta E from vCSF were significantly lower in patients who had received intravenous administration of morphine sulfate (48.4 +/- 5.8 versus 85.9 +/- 10.1 pg/ml, P = 0.008). No correlation was found between vCSF levels of ir-beta E and elapsed time after injury. Although vCSF and serum ir-beta E were correlated (r = 0.532, P = 0.050), the latter exhibited a different profile; the mean level of serum ir-beta E was not significantly different in those patients who received morphine, and serum ir-beta E had a significant negative correlation with time after injury (r = -0.587, P = 0.03). These results do not support a relationship between acute levels of vCSF or serum ir-beta E and the degree of neurological injury or outcome after severe head trauma. This article, therefore, is a contribution to the body of literature in which the purported detrimental effect of beta-endorphin was not demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Possible protective effect of endogenous opioids in traumatic brain injury.

Naloxone (0.1, 1.0, or 20.0 mg/kg), morphine (1.0 or 10.0 mg/kg), or saline was administered systemically intraperitoneally to rats 15 minutes prior to moderate fluid-percussion brain injury. The effects of the drugs were measured on systemic physiological, neurological, and body-weight responses to injury. The animals were trained prior to injury and were assessed for 10 days after injury on body-weight responses and neurological endpoints. Low doses of naloxone (0.1 or 1.0 mg/kg) significantly exacerbated neurological deficits associated with injury. Morphine (10.0 mg/kg) significantly reduced neurological deficits associated with injury. The drugs had no effect on neurological measures or body weight in sham-injured animals. Drug treatments did not significantly alter systemic physiological responses to injury. Data from these experiments suggest the involvement of endogenous opioids in at least some components of neurological deficits following traumatic brain injury and suggest the possibility that at least some classes of endogenous opioids may protect against long-term neurological deficits produced by fluid-percussion injury to the rat.

Animals↗
PubMed1989

Afferent and efferent connections of the cholinoceptive medial pontine reticular formation (region of the ventral tegmental nucleus) in the cat.

Following minor concussive brain injury when there is an otherwise general suppression of CNS activity, the ventral tegmental nucleus of Gudden (VTN) demonstrates increased functional activity (32). Electrical or pharmacological activation of a cholinoceptive region in this same general area of the medial pontine tegmentum contributes to certain components of reversible traumatic unconsciousness, including postural atonia (31, 32, 45). Therefore, in an effort to examine the neuroanatomical basis of the behavioral suppression associated with a reversible traumatic unconsciousness, the afferent and efferent connections of the VTN and putative cholinoceptive medial pontine reticular formation (cmPRF) were studied in the cat using the retrograde horseradish peroxidase (HRP), HRP/choline acetyltransferase (ChAT) double-labeling immunohistochemistry, and anterograde HRP and autoradiographic techniques. Based upon retrograde HRP labeling, the principal afferents to the VTN region of the cmPRF originated from the medial and lateral mammillary nuclei, and lateral habenular nucleus, and to a lesser extent from the interpeduncular nucleus, lateral hypothalamus, dorsal tegmental nucleus, superior central nucleus, and contralateral nucleus reticularis pontis caudalis. Other afferents, which were thought to have been labeled through spread of HRP into the medial longitudinal fasciculus (MLF), adjacent paramedian pontine reticular formation, or uptake by transected fibers descending to the inferior olive, included the nucleus of Darkschewitsch, interstitial nucleus of Cajal, zona incerta, prerubral fields of Forel, deep superior colliculus, nucleus of the posterior commissure, nucleus cuneiformis, ventral periaqueductal gray, vestibular complex, perihypoglossal complex, and deep cerebellar nuclei. In HRP/ChAT double labeling studies, only a very small number of cholinergic VTN afferent neurons were found in the medial parabrachial region of the dorsolateral pontine tegmentum, although the pedunculopontine and laterodorsal tegmental nuclei contained numerous single-labeled ChAT-positive cells. Anterograde HRP and autoradiographic findings demonstrated that the VTN gave rise almost exclusively to ascending projections, which largely followed the course of the mammillary peduncle (16,21) and medial forebrain bundle, or the tegmentopeduncular tract (4). The majority of fibers ascended to terminate in the medial and lateral mammillary nuclei, interpeduncular complex (especially paramedian subnucleus), ventral tegmental area, lateral hypothalamus, and the medial septum in the basal forebrain. Labeling that joined the mammillothalamic tract to terminate in the anterior nuclear complex of the thalamus was thought to occur transneuronally. Some projections were also observed to nucleus reticularis pontis oralis and caudalis, superior central nucleus, and dorsal tegmental nucleus adjacent to the VTN...

Animals↗
PubMed1989

Effect of D, alpha-tocopheryl succinate and polyethylene glycol on performance tests after fluid percussion brain injury.

One hundred and one rats were administered either D, alpha-tocopheryl succinate plus polyethylene glycol (PEG), PEG, or saline 30 min prior to or 5 min after moderate fluid percussion brain injury. Mortality rates, performance on beam balance and beam-walking tasks, and body weight were assessed daily for 10 days. With preinjury administration, mortality rate was reduced from 31% with saline to 9% with PEG and 9% with D, alpha-tocopheryl succinate plus PEG. With postinjury administration, mortality rate was reduced from 36% with saline to 20% with PEG and to 10% with the D, alpha-tocopheryl succinate plus PEG combination. With administration prior to injury, PEG and D, alpha-tocopheryl succinate plus PEG reduced the deficits seen on beam balance testing on days 1-3 after injury. On beam walking, PEG and D, alpha-tocopheryl succinate plus PEG reduced deficits compared to those in saline-injected animals on days 1 and 2 and on day 1 after injury, respectively. A strongly protective effect of PEG and of D, alpha-tocopheryl succinate plus PEG was seen with preinjury administration. With postinjury administration, D, alpha-tocopheryl succinate plus PEG reduced deficits on beam balance testing compared to animals receiving both saline and PEG on days 1-3 after injury. On beam-walking latencies, D, alpha-tocopheryl succinate plus PEG reduced deficits on days 1 and 2 after injury compared to saline and to PEG. Both PEG and D, alpha-tocopheryl succinate plus PEG reduced weight loss after injury compared to saline. The protective effects of these agents and their relatively low toxicity and high lipid solubility give them potential for the treatment of human head injury.

Animals↗
PubMed1988

Effects of scopolamine treatment on long-term behavioral deficits following concussive brain injury to the rat.

Scopolamine (0.1, 1.0, or 10.0 mg/kg) or saline was systemically (i.p.) administered to rats 15 min prior to concussive fluid percussion brain injury. Animals pretreated with the 1.0 mg/kg dose exhibited significantly (P less than 0.05) less motor deficits and less body weight loss and recovered to baseline performance sooner than saline-treated rats. Mortality and associated convulsions were significantly lower in rats pretreated with the 1.0 mg/kg dose of scopolamine. A 1.0 mg/kg dose of scopolamine administered (i.p.) 30 s after injury also significantly reduced behavioral deficits. No differences were observed between saline- and scopolamine-treated animals in either the incidence or duration of transient apnea following injury. A 1.0 mg/kg dose of scopolamine administered (i.p.) 15 min prior to epidural clip compression of the spinal cord had no effect on the severity of motor function deficits assessed by an inclined plane test. The data from these experiments suggest muscarinic cholinergic involvement in at least some of the long-term behavioral deficits following mild and moderate levels of brain injury. These results suggest that muscarinic cholinergic antagonists may prove beneficial in the treatment of human head injury.

Animals↗
PubMed1988

The effect of concussive head injury on central cholinergic neurons.

This study examined the effect of fluid percussion head injury on the activity of cholinergic neurons in specific brain areas of the rat 12 min, 4 h and 24 h following injury. Acetylcholine (ACh) turnover, used as an index of cholinergic neuronal activity, was determined using a gas chromatographic-mass spectrometric technique. The most striking changes in cholinergic activity were observed in the dorsal pontine tegmentum, where concussive head injury produced an increase in ACh turnover 12 min and 4 h following injury. This area has been previously associated with behavioral changes observed following concussive injury. ACh turnover in the thalamus, a region to which pontine cholinergic neurons project, also tended to increase 4 h following injury. On the other hand, ACh turnover tended to decrease in the amygdala 4 h following injury. Although there were no significant changes in hippocampal ACh content or turnover following injury. ACh content did tend to increase in that brain region 12 min following injury. There were no significant effects of injury on cholinergic neurons in the cingulate/frontal cortex. These changes in cholinergic neuronal activity may contribute to the neurological deficits following concussive injury. In particular, activation of cholinergic neurons in the pontine region may contribute to components of behavioral suppression associated with reversible traumatic unconsciousness. More generalized changes in cholinergic function may lead to the production of more chronic deficits.

Acetylcholine↗
PubMed1988

Effects of anticholinergic treatment on transient behavioral suppression and physiological responses following concussive brain injury to the rat.

Increasing doses (0.1, 1.0, 10.0 mg/kg) of scopolamine were systemically (i.p.) administered to rats subjected to moderate fluid percussion brain injury. Scopolamine treatment (1.0 mg/kg, i.p.) 15 min prior to trauma significantly reduced mortality and the duration of transient behavioral suppression assessed by a variety of measures. No differences were observed between saline- and scopolamine-treated animals in either the incidence or duration of transient apnea associated with injury. Preinjury treatment with methylscopolamine (1.04 mg/kg) or mecamylamine (1.0 mg/kg) had no effect on transient behavioral suppression. Except for increased heart rate, preinjury treatment with scopolamine (1.0 mg/kg) did not significantly alter systemic physiological responses to injury. Rats treated with scopolamine (1.0 mg/kg, i.p.) 30 s after injury tended to have shorter durations of reflex and response suppression. These experiments suggest that antimuscarinics can attenuate components of transient behavioral suppression associated with concussive brain injury. These findings are consistent with previous experimental and clinical observations and lend further support to the hypothesis that activation of a muscarinic system within the CNS mediates components of reversible traumatic unconsciousness following cerebral concussion.

Animals↗
PubMed1988

Regional rates of glucose utilization in the cat following concussive head injury.

Injections of [14C]-deoxyglucose ([14C]DG) were used to study rates of local cerebral glucose utilization (LCGU) in control cats and cats subjected to concussive brain injury produced by a fluid-percussion device. Studies in separate groups of animals demonstrated that the injury level selected produced transient behavioral suppression probably associated with traumatic disturbances of consciousness. LCGU was sampled near the site of fluid-percussion injury and more caudally in pontine regions. Histopathologic studies examined the possibility of hemorrhage, contusion, or breakdown of the blood-brain barrier in regions within which LCGU was calculated. These studies yielded analyses indicating that (1) the [14C]DG technique can be applied usefully to infer changes in regional levels of brain activity after concussion, (2) concussive injury produces changes in brain function that differ reliably across various regions of the central nervous system and may include both depression and focal activation of specific brain sites. Data are discussed that suggest that changes in brain activity in specific regions indicated by changes in LCGU could contribute to acute neurologic disturbances after concussion including unconsciousness.

Animals↗
PubMed1988

The effects of scopolamine and traumatic brain injury on central cholinergic neurons.

This study examined the effects of scopolamine and fluid percussion traumatic brain injury (TBI) on the activity of cholinergic neurons in specific areas of the rat brain 12 min, 4 h, and 24 h after injury. Acetylcholine (ACh) turnover, used as an index of cholinergic neuronal activity, was determined using gas chromatography-mass fragmentography. Scopolamine pretreatment prevented significant increases in dorsal pontine ACh turnover at 12 min and 4 h after TBI, suggesting that the drug's protective actions against the neurologic deficits following TBI may involve blockade of cholinergic neuronal activation as well as postsynaptic muscarinic blockade. The responses of thalamic, hippocampal, and amygdaloid cholinergic neurons to TBI did not differ substantially in scopolamine-pretreated rats from those studied previously in untreated fluid-percussion-injured rats. However, cholinergic neurons in the cingulate-frontal cortex of rats receiving TBI did respond in a different manner to scopolamine than those of rats receiving sham injury, suggesting a disruption of regulation of cortical cholinergic neurons following this model of TBI.

Acetylcholine↗
PubMed1988

Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury.

This study examined the effects of pretreatment with phencyclidine (PCP), a selective N-methyl-D-aspartate (NMDA) antagonist, on behavioral and physiologic responses of the rat to experimental traumatic brain injury (TBI). For the behavioral experiments, rats were administered either saline or PCP (1.0, 2.0, or 4.0 mg/kg, intrapentoneally [IP] 15 min before TBI. Rats were ventilated as necessary following injury. The duration of acute suppression of several reflexes (pinna, corneal, righting, and flexion) and responses (escape, head support, and spontaneous locomotion) was recorded for up to 70 min after trauma. Longer-term behavioral assessments (beam walking, beam balance, inclined plane, ambulatory activity, and body weight) were made for up to 10 days after trauma. PCP did not significantly alter the duration of acute behavioral suppression. At a dosage of 1.0 mg/kg, PCP significantly attenuated all long-term deficits except beam walking. Maximal protection against beam walking deficits was provided by the 4.0 mg/kg dosage of PCP. Sixty-three percent of saline-treated animals died within 10 days after injury. For rats pretreated with 1.0, 2.0, and 4.0 mg/kg of PCP, 40%, 23%, and 33% died, respectively. In physiologic experiments, pretreatment with 4.0 mg/kg of PCP (IP) 15 min before injury did not significantly affect systemic cardiovascular responses, plasma glucose levels, or blood gas levels observed within 30 min after injury. While the possibility of effects mediated by other neurotransmitter systems cannot be excluded, these data suggest that NMDA agonist-receptor interactions contribute to the pathophysiology of brain injury. In addition, neural mechanisms that mediate transient unconsciousness following moderate levels of head injury may differ from mechanisms that mediate more persistent neurologic deficits.

Animals↗
PubMed1988

Combined pretrauma scopolamine and phencyclidine attenuate posttraumatic increased sensitivity to delayed secondary ischemia.

Fasted Wistar rats were given a mild level of traumatic brain injury (TBI) and then subjected to 6 min of transient forebrain ischemia 24 h posttrauma. One group was given simultaneous 1 mg/kg scopolamine and 4 mg/kg phencyclidine intraperitoneally (IP) 15 min before trauma and another group an equal volume of plasmalyte A solution. After 7 days of postinjury survival, placebo-treated rats demonstrated increased posttraumatic vulnerability to secondary ischemic CA1 neuronal death even 24 h after trauma. This finding confirmed that increased posttraumatic ischemic vulnerability persists for at least 24 h even following mild trauma. Combined muscarinic receptor and N-methyl-D-aspartate (NMDA) receptor coupled ion channel blockade given and present during the mild TBI statistically attenuated this enhanced secondary ischemic CA1 neuronal death and thus posttraumatic increased ischemic vulnerability. Placebo-treated rats had 335.3 +/- 93.6 CA1 neurons/10(6) microns 2 and drug-treated rats had 844.8 +/- 184.9 CA1 neurons/10(6) microns 2. This result suggests that muscarinic and/or NMDA receptor-mediated events confined to TBI and the early posttraumatic period are in part responsible for the phenomenon of increased posttraumatic ischemic vulnerability.

Animals↗
PubMed1988

Experimental traumatic brain injury elevates brain prostaglandin E2 and thromboxane B2 levels in rats.

Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) levels were measured in rats following experimental traumatic brain injury. Rats (n = 36) were prepared for fluid percussion brain injury under pentobarbital anesthesia. Twenty-four hours later, rats were lightly anesthetized using methoxyflurane, injured (2.3 atm), and killed 5 or 15 min later. Twelve of the rats died before and are not included in the analyses. The following groups were used for data analysis: group I (n = 6) were sham-injured rats prepared for injury but not injured: group II (n = 6) were injured and killed 5 min later; group III (n = 12) were injured and killed 15 min posttrauma. Thirty seconds prior to sacrifice by decapitation into liquid nitrogen, all rats were injected with indomethacin (3 mg/kg, intravenously [IV]) to prevent postmortem PG synthesis. After sacrifice, brains were removed, weighed, and homogenized in a small quantity of phosphate buffer with indomethacin (50 micrograms/ml). PGE2 and TxB2 levels were determined using double-label radioimmunoassays. Posttraumatic convulsions were observed in 5 of 12 rats in group III and these rats were analyzed separately. PGE2 and TxB2 levels increased significantly (p less than 0.05) in both hemisphere and brainstem 5 min posttrauma. Fifteen minutes after injury, both PGE2 and TxB2 levels remained elevated but the levels were lower than at 5 min in the rats that did not exhibit posttraumatic seizures. This decrease in PG levels at 15 min was not observed in the rats that had seizures after injury and both PGE2 and TxB2 levels remained high in hemispheres and brainstem. Thus, fluid percussion brain injury results in substantial elevations in PGE2 and TxB2 levels and posttraumatic seizures exacerbate the observed increases.

Animals↗
PubMed1988

Changes in regional brain acetylcholine content in rats following unilateral and bilateral brainstem lesions.

Previous research (Adametz, 1959) has shown that two-step bilateral lesions of the reticular formation in cats produce minimal behavioral disruption compared to one-step bilateral lesions, which produce profound behavioral suppression. We systematically examined alterations in forebrain acetylcholine (ACh) content and neurologic tolerance to one-step and two-step bilateral and unilateral lesions of the pontomesencephalic reticular formation (PMRF) in rats. One-step and two-step bilateral lesions separated by 1 or 5 days produced irreversible bilateral motor dysfunction. Survival after lesioning was 10%, 20%, and 0%, respectively. Unilateral lesion or two-step bilateral lesions separated by 15 or 30 days produced transient (less than 3 days) contralateral motor dysfunction. Survival after lesioning was 90%, 90%, and 100%, respectively. Within 24 h after one-step bilateral lesions, ACh content was significantly decreased bilaterally in thalamus, frontal cortex, amygdala, hippocampus, and basal forebrain. Within 5 days after unilateral lesioning, ACh content was significantly decreased ipsilaterally in the thalamus, amygdala, and hippocampus and had returned to control values by day 10 in the thalamus and hippocampus. The increased neurologic tolerance and recovery of ACh content in two-step bilateral PMRF lesions demonstrate important functional and neurochemical plasticity to brain injury. Although not directly addressing mechanisms of neural plasticity, this research examined possible associations between neurologic tolerance to PMRF lesions and neurochemical markers of forebrain ACh activity.

Acetylcholine↗
PubMed1988

Cytokines involved in the generation of cytolytic effector T lymphocytes.

The differentiation of precursor, antigen-competent, T cells into effective helper and/or cytolytic cells involves a number of different steps that are signaled by soluble molecules termed cytokines. We demonstrate here that subsets of T cells, distinguished on the basis of their expression of cell-surface markers, CD4 and CD8, receive distinct signals for differentiation. The precursor T cells of a T-cell subset that is MHC class II-restricted are readily activated by signals provided by rIL-1, rIL-2, rIL-3, or IFN-gamma. The precursor T cells of the MHC class I-restricted T-cell subset, on the other hand, are not readily activated by signals provided by rIL-1, rIL-3, or IFN-gamma. Recombinant IL-2 apparently functions in a nonrestricted manner, in that it can provide growth signals to both MHC class I- and class II-restricted T cells.

Animals↗
PubMed1987

The origin of brainstem afferents of the paramedian pontine reticular formation in the cat.

Transcannular microinjections of horseradish peroxidase (HRP) were made into the paramedian pontine reticular formation (PPRF) in adult cats to determine the origin of the principal sources of inputs to this important preoculomotor center for the production of saccadic eye movements. Retrogradely labeled cells were observed in numerous oculomotor-related structures, including the prerubral field (rostral interstitial nucleus of the medial longitudinal fasciculus), nucleus of Darkschewitsch, nucleus of the posterior commissure, deep superior colliculus, supraoculomotor ventral periaqueductal gray, contralateral paramedian pontine reticular formation, pontine raphe and dorsal medial pontine tegmentum medial to the abducens nucleus (purported to contain omnipause neurons), cell group Y, and the perihypoglossal complex (nucleus prepositus hypoglossi). Other sources of afferents to the region included the zona incerta, lateral and medial habenular nuclei, medial hypothalamus, medial mammillary nucleus, nucleus cuneiformis, medial medullary reticular formation, and the medial and lateral cerebellar nuclei. The results are discussed in terms of the potential influence of these nuclei on the control of eye movement.

Afferent Pathways↗