Biomedical subjects

K H Reid

Publications and source records attributed to K H Reid.

At least 19 recordsLinked to original sources

PubMed2003

Experience with ketamine and sodium pentobarbital as anesthetics in a rat model of cardiac arrest and resuscitation.

We review 7 years experience with the chest compression model of cardiac arrest and resuscitation, comparing two different anesthetics. Ketamine stimulates cardiac function and only mildly depresses respiration; of the two it provides easier resuscitation. However, ketamine severely depresses brain protein synthesis; in studies using this measure ketamine is unsuitable and another agent must be used. Sodium pentobarbital mildly depresses brain protein synthesis, but depresses both cardiac and respiratory function, making resuscitation more difficult. Use of alternate chest/abdominal pumping (Babbs resuscitation technique), with judicious use of intra-cardiac epinephrine (adrenaline), made resuscitation reliable under sodium pentobarbital as well.

Anesthetics, Dissociative↗

PubMed2001

The mRNA level of the potassium-chloride cotransporter KCC2 covaries with seizure susceptibility in inferior colliculus of the post-ischemic audiogenic seizure-prone rat.

Cardiac arrest and resuscitation were used to induce brain damage and susceptibility to sound-triggered seizures in Sprague-Dawley rats. Glucose preloading was used to vary seizure susceptibility. Because loop diuretics can block these seizures, we investigated changes in KCC2, a potassium-chloride cotransporter, in the inferior colliculus - the origin of the seizures. Using polymerase chain reaction (PCR), we found that collicular KCC2 mRNA levels covaried with seizure susceptibility in these animals. Using quantitative PCR, we found that a fivefold increase in collicular KCC2 mRNA levels was associated with a doubling of seizure incidence. A hypothesis linking KCC2 activity to seizure susceptibility is presented.

Animals↗

PubMed2000

Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats.

The purpose of this study was to determine whether the loop diuretics furosemide, bumetanide and ethacrynic acid, which block the KCC1 potassium-chloride transporter in the kidney loop of Henle and the KCC2 potassium-chloride transporter in neuronal membranes, would prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. The rats were infused with the test agent via tail vein shortly before being tested for seizure susceptibility by exposure to loud noise (an alarm bell) for 60 s. Sound exposures were repeated at intervals to determine the time course of the seizure suppression effect. All three loop diuretics suppressed sound-triggered seizures in post-ischemic rats tested 2 days to 4 weeks after the ischemic exposure. Furosemide 200 mg/kg had no effect in 4/4 rats made acutely audiogenic seizure-prone by infusion of bicuculline into the inferior colliculus, indicating that the effect was not due to general anti-seizure activity. Mannitol 2 g/kg had no effect in 6/6 post-ischemic rats, indicating that the effect was not due to diuresis or fluid shifts. These results are consistent with the hypothesis that the exposure to global ischemia caused an upregulation of the potassium-chloride transporter KCC2 in neurons which persisted for at least 4 weeks.

Acoustic Stimulation↗

PubMed1999

Correlates of delayed neuronal damage and neuroprotection in a rat model of cardiac-arrest-induced cerebral ischemia.

Numerous studies over the past three decades have used rodent models of cerebral ischemia. To measure the postischemic outcome, the majority of these studies used histopathology as the method of choice both quantitatively and qualitatively. No functional measure of postischemic outcome has been proved to correlate well with the histopathological one. The rat chest compression model of cardiac-arrest-induced global cerebral ischemia was used in the present study. Two separate measures of neuronal damage at 7 days postischemia were performed: (a) histologically, by counting normal pyramidal cell bodies in the mid-CA1 hippocampal region of the rat brain, in hematoxylin-eosin-stained, paraffin-embedded 6-microm sections, and (b) electrophysiologically, by counting the number of 400 microm hippocampal slices in which it was possible to evoke a normal (>/=10 mV) CA1 population spike by orthodromic stimulation of the Schaffer collaterals. The correlation between these two measures was tested in the following groups of rats: (a) control, untreated group, (b) MK-801-treated groups (0.03 to 1.0 mg/kg given i.p. shortly after ischemia), (c) diltiazem-treated (DILT) groups 1.0 to 30 mg/kg, given i.p. shortly after ischemia, and (d) a group treated with a combination of the two drugs together (0.1 mg/kg MK-801+3.0 mg/kg DILT given i.p. shortly after ischemia). The two measures of postischemic outcome were highly correlated in all groups studied. Both MK-801 and DILT exhibited a dose-dependent neuroprotective effect. When administered together, a synergy between the neuroprotective effect of MK-801 and DILT was observed. At the doses used, minimal or no side effects of either MK-801 or DILT were observed.

Animals↗

PubMed1998

Fosphenytoin reduces hippocampal neuronal damage in rat following transient global ischemia.

Fosphenytoin, a water-soluble disodium phosphate ester of phenytoin, is a phenytoin prodrug with similar anticonvulsant properties. In this study, we evaluated its neuroprotective properties in a cardiac arrest-induced global ischemia model. After 12 minute ischemia, Long-Evans hooded rats were resuscitated, given fosphenytoin (30 mg/kg, i.m.) or saline 5 minutes after the ischemic episode, and killed on day 7. Brains were removed, fixed, and vibratome sectioned to assess the numbers of normal appearing CAI pyramidal neurons and for immunohistological staining of glial fibrillary acidic protein (GFAP). After global ischemia, the number of hippocampal CA1 pyramidal neurons decreased significantly (from 14.33 +/- 1.73 to 2.19 +/- 0.16 per 100 micron 2). Most hippocampal CA1 pyramidal neurons showed signs of injury and GFAP immunoreactivity of the region increased. With fosphenytoin treatment 5 min after ischemia, hippocampal CA1 pyramidal neurons remained at near control level (13.90 +/- 0.92), however, GFAP staining was not significantly changed. Our data, although indicating different neuronal and glial responses following fosphenytoin treatment, nevertheless, suggest that fosphenytoin is an effective neuroprotectant against ischemia-induced damage.

Analysis of Variance↗

PubMed1998

Changes in brainstem auditory evoked response latency predict survival after CPR in a rat model of cardiac arrest and resuscitation.

Brainstem auditory evoked responses (BAER) are routinely used to monitor brainstem function in hospitalized comatose patients. We used a rat model of cardiac arrest and resuscitation to explore the possibility that the BAER, monitored during and immediately after cardiopulmonary resuscitation (CPR), could be used to determine whether the CPR was effective in restoring brainstem blood flow. Long-Evans rats were subjected to 7 min of cardiac arrest, induced by chest compression under Ketamine anesthesia sufficient to mechanically prevent the heart from pumping blood and were then resuscitated using a standard CPR protocol. During CPR, click stimuli were applied to one ear at 11/s and BAER averages recorded every 15 s. In three rats the BAER did not return after CPR; none of these rats respired spontaneously and all died. In 33 rats the BAER did return; within 15 min after the start of CPR BAER peak latencies decreased rapidly, increased again and then decreased. If the increase in the latency of the N2 peak was less than 0.3 ms, then the rat survived. If it was greater than 0.35 ms the rat died. This signal was used as a cue for intervention in three rats; two survived. Thus, in this preparation, the BAER provided a useful measure of CPR effectiveness, in time to permit successful intervention.

Animals↗

PubMed1998

Carbon dioxide narcosis-induced apnea in a rat model of cardiac arrest and resuscitation.

In the clinical literature there are reports of patients failing to breathe and becoming comatose when supplied with 100% oxygen for respiratory distress. This effect has been attributed to a loss of respiratory drive. Recent studies have established that this explanation is incorrect, but have left the phenomenon unexplained. We propose that the apnea and coma reported is due to carbon dioxide narcosis. We have reproduced this effect in an animal model and have documented PCO2 values in excess of 250 mmHg during the apneic period. Our results suggest that this level of PCO2 suppresses both brainstem auditory evoked potentials and spontaneous respiration. The high PCO2 is due to inadequate gas exchange, and is easily remedied by provision of adequate ventilation.

Animals↗

PubMed1997

Ischemia-induced anxiety following cardiac arrest in the rat.

Male Long-Evans rats were subjected to 7 min of chest compression (CC) to produce cardiac arrest and global ischemia resulting in damage to the brain. Timidity and motor activity were evaluated using the elevated plus maze, one of the most widely accepted methods for measuring anxiety in rats. Post-ischemic rats spent much less time in the open arms (3% at day 5) than handled (54%) or sham-compressed (30%) rats. This was interpreted as increased anxiety. Thus, post-ischemic rats developed more anxiety than normal handled rats or sham-operated rats. Anxiety increased markedly on post-ischemic day 2, suggesting a delayed effect. Anxiety gradually decreased after day 5 but recovery was still incomplete up to 115 days post-ischemia. Motor activity decreased gradually during days 2-5 post-ischemia and then recovered to the normal range after day 15. These results are inconsistent with damage limited to the hippocampus and suggest that less obvious histological changes may be occurring elsewhere in the brain.

Animals↗

PubMed1997

Fos-like immunoreactivity in rat hippocampal neurons following transient global ischemia.

Immediate early genes are expressed following ischemia in many tissues including the brain. Using a chest compression global ischemia model that produced delayed neuronal degeneration in surviving rats, we examined the hippocampal Fos response to ischemia/reperfusion by immunohistochemistry and electron microscopy. Immunostained nuclei were seen in a few CA1 pyramidal cells 1-3 h after reperfusion while the entire dentate granular cell population was immunoreactive. By electron microscopy, subcellular Fos-like immunoreactive sites were found both in the cell nuclei and on segments of endoplasmic reticulum. These findings indicate that transient global ischemia differentially affects the early response genes in neurons of the hippocampal subfields and that such difference may be related to the adult neuroplasticity of the brain.

Animals↗

PubMed1996

Audiogenic seizures following global ischemia induced by chest compression in Long-Evans rats.

Transient global ischemia was used to produce a rat model of generalized tonic-clonic epilepsy. Controlled chest compression in ketamine-anesthesized Long-Evans rats produced transient global ischemia by mechanically preventing the heart from pumping blood. Circulation was restored by standard cardiopulmonary resuscitation techniques. With a temporal muscle (skull) temperature of 35 +/- 0.4 degrees C, 75% (76/102) of the rats survived 7 min of chest compression. Generalized seizures could be evoked in 78% (59/76) of the surviving rats by a 60 s exposure to a loud sound (bell, 110 dB) beginning 24 h after the ischemic episode. The seizure patterns seen resembled those described by Maresceaux (1987) for genetically seizure-prone Wistar rats. Susceptibility to sound-induced seizures declined with time, with wide variations in recovery rate between individuals; one rat showed a daily sound-induced seizure for over 5 months. Seizures were attenuated or blocked by treatment with carbamazepine or sodium valproate. This model is similar to the great vessel occlusion model used by Kawai et al. (1995), but is less invasive. We believe it will be useful in the evaluation of therapies for acquired generalized (grand mal) seizures.

Acoustic Stimulation↗

PubMed1995

Chemical traumatization of adult mouse olfactory epithelium in situ stimulates growth and differentiation of olfactory neurons in vitro.

This study demonstrates that ZnSO4-induced chemical trauma results in an in situ regeneration of the olfactory epithelium which, when maintained in vitro, provides an enriched population of olfactory neurons. Therefore, the ability of the olfactory epithelium to respond to chemical trauma with increased mitotic activity can be used to increase growth of neurons in culture. Tissue obtained from normal or vehicle-treated adult mice produced few olfactory neurons, when maintained in culture, compared to cultures established from tissue following an in situ ZnSO4 trauma. Maximal neuronal yields were obtained in cultures established from tissue that was removed 4-6 days following chemical trauma. The morphological appearance and the presence of cell specific intermediate filament proteins were used to classify the cell types in these olfactory epithelial cultures. Single cells and aggregates of cells which were immunopositive for keratin, but immunonegative for neurofilament protein and GFAP, were identified as epithelioid. Flattened polygonal cells immunopositive for GFAP were identified as glia. A small population of flattened cells was immunonegative for all of the antibodies used in this study. Cells that had processes were immunonegative for GFAP and keratin. Some were immunopositive for 200 kDa and 160 kDa neurofilament proteins but immunonegative for the 68 kDa neurofilament protein. A few of these cells showed positive immunoreactivity with the olfactory marker protein (OMP) antibody and most likely represented the most mature olfactory neurons in the cultures. This trauma-induced culture model using olfactory tissue from adult mice can serve as a source of CNS neurons for comparison with cultured embryonic neurons.

Animals↗

PubMed1995

Cardiac arrest-induced global cerebral ischemia studied in vitro.

The goal of the present study was to characterize the effects of chest compression-induced global cerebral ischemia on the hippocampal slice preparation. One of the characteristics of rats exposed to such cardiac arrest is a high susceptibility to sound-induced seizures. We tested audiogenic seizures as an in vivo indicator of ischemic cerebral damage and as a possible small animal model of epilepsy. The results of these tests were reported elsewhere. Long-Evans male rats (200-350 g) were subjected to 7 min of chest compression sufficient to stop the pumping action of the heart. The rats were then revived using cardiopulmonary resuscitation. Evaluation of cerebral damage following cardiac arrest and resuscitation was performed in vitro, by testing neuronal responses to electrical stimulation in hippocampal slices prepared from these animals. Sham control animals were used for comparisons. Twenty-one to 146 days after rats were chest-compressed, hippocampal slices were prepared. Sham control rats, anesthetized but not chest-compressed, were sacrificed one week later for preparation of slices. Rats in a second group exposed to 7-min chest compression, were sacrificed at different time intervals after their resuscitation (from 1 h to 7 days); hippocampal slices were prepared for electrophysiological analysis of neuronal damage. The results of these studies indicate that 3 weeks or longer after chest compression the evoked CA1 population spike amplitude in hippocampal slices was significantly attenuated; in 60% of these slices an epileptiform response was evoked. An increased proportion of slices prepared from rats 1 to 48 h after chest compression showed an augmentation in the amplitude of the evoked population spike; 72 h and up to 7 days after chest compression, an attenuation in the evoked CA1 population spike amplitude was observed, signaling delayed neuronal damage.

Animals↗

PubMed1995

Early, but not late, antiepileptic treatment reduces relapse of sound-induced seizures in the post-ischemic rat.

Global ischemia was used to induce a sensitivity to sound-triggered generalized seizures in 24 male Long-Evans rats. All showed a generalized seizure when exposed to a 108 dB bell for 1 min. They were assigned randomly to 3 groups of 8, and received 30 additional sound exposures. The early treatment group was injected with valproate (200 mg/kg i.p) 1 h prior to each of the first 10 sound exposures. The late treatment group received the same treatment during the second set of 10 sound exposures after 10 sound exposures without treatment. The third group was untreated. Both early and late treated groups had a significant reduction in seizure incidence during the treatment period, i.e. both groups showed seizure control. However, in the late group seizures returned promptly when valproate treatment was discontinued, while the early group showed a sustained reduction in seizure susceptibility. Since this outcome corresponds to seizure remission, the findings of this study favor early treatment.

Acoustic Stimulation↗

PubMed1994

Administration of human chorionic gonadotropin affects sleep-wake phases and other associated behaviors in cycling female rats.

We investigated the possible effects of human chorionic gonadotropin (hCG) on sleep-wake phases and other associated behaviors controlled by the medial preoptic area, cerebral cortex and hippocampus. Chronic epidural electroencephalographic (EEG) and temporal muscle electromyographic (EMG) electrodes were placed in cycling female rats. After a week of recovery, rats were injected intraperitoneally at 3.00 pm on the day of proestrus with either saline or highly purified hCG or indomethacin or hCG plus indomethacin. Three hours after injection, EEG, EMG and behavioral activities were recorded for 3.5 h. The administration of hCG increased high and low amplitude sleep, resting phase and decreased active awake phase, walking, sniffing and chewing as compared to the controls. While the administration of indomethacin alone had no effect, coadministration inhibited hCG effects. Medial preoptic area, cerebral cortex and hippocampus contain immunostaining for LH/hCG receptors. The administration of hCG resulted in an increase of immunoreactive PGD2 and a decrease of PGE2 in median preoptic area, cerebral cortex and hippocampus as compared to the controls. In summary, hCG administration affects sleep-wake phases and other associated behaviors in rats which can collectively be described as decreased activity. These effects are probably mediated by increasing PGD2 and decreasing PGE2 in areas of brain which control these activities. The above findings may be relevant to pregnant women who experience decreased activity when hCG is present in the circulation and cerebrospinal fluid.

Alprostadil↗

PubMed1994

Stability of thrombosis induced by electrocoagulation of rat middle cerebral artery.

BACKGROUND AND PURPOSE: Although it is often assumed in experimental stroke studies that cautery-induced occlusion is permanent, surgeons commonly expect cauterized vessels to recanalize spontaneously. We used the rat middle cerebral artery to determine if electrocoagulation would produce a permanent occlusion in this preparation. METHODS AND RESULTS: A standard bipolar coagulator, calibrated to determine actual power output, was adjusted to induce platelet aggregation in the middle cerebral artery of anesthetized Sprague-Dawley rats without inducing bleeding through the arterial wall. A reliable temporary thrombosis was induced by a Malis Bipolar Coagulator set to deliver 10 bursts of 1.5 seconds each at a rate of 24 min-1 and a power setting of 3 W. This thrombus was responsive to the antithrombotic agent flunarizine. An apparently permanent occlusion was produced by 30 bursts at 3 W followed by 20 bursts at 5 W. To our surprise, seven of seven such occlusions recanalized spontaneously within 4 hours. CONCLUSIONS: The electrocoagulation process commonly used in experimental stroke studies may produce only a temporary occlusion of the rat middle cerebral artery.

Animals↗

PubMed1993

Dimethylsulfoxide (DMSO) blocks conduction in peripheral nerve C fibers: a possible mechanism of analgesia.

Dimethylsulfoxide (DMSO) is readily absorbed through skin, and relieves musculoskeletal pain when applied topically to painful areas. We studied the effects of DMSO on C-type nerve fibers, which mediate pain sensation. DMSO was applied directly to exposed cat sural nerves. C fiber conduction velocity was slowed by DMSO, even in low concentrations (5-7% v/v). Higher concentrations completely blocked C fiber conduction, with a minimum blocking concentration of 9%. Onset of nerve block was almost immediate with 15% DMSO or higher concentrations. C fiber blockade may account for analgesia with DMSO.

Action Potentials↗

PubMed1991

The focally demyelinated rat fimbria: a new in vitro model for the study of acute demyelination in the central nervous system.

We have produced controlled local demyelination in Wistar rat fimbriae by injection of microliter quantities of the detergent lysophosphatidyl choline (LPC) stereotactically. Six to seven days later the hippocampus and fornix was dissected out en bloc and maintained in vitro for electrical evaluation of conduction through the damaged area. The tissue was then fixed for verification of the lesion by light and electron microscopy. All fimbriae showed a normal conducted action potential with a latency of 0.5 to 1.5 ms when the conduction distance was 4-5 mm. LPC-lesioned fimbriae also showed a later wave with a latency of 4-5 ms. This later wave had the same stimulus-response curve as the primary action potential, but was more sensitive to repeated stimulation. We interpret this wave as evidence of conduction into or through a demyelinated region. LPC-lesioned fimbriae also showed histological evidence of demyelination. This preparation provides an in vitro model for the study of acute local demyelination of central nervous system white matter, such as that induced by multiple sclerosis and other focally demyelinating diseases.

Acute Disease↗

PubMed1991

Increasing extracellular calcium improves conduction in partially demyelinated rat fimbria in vitro.

1. We have tested the effect of changed concentrations of Ca2+ upon demyelination-induced conduction block in rat fimbria in vitro. 2. In a rat fimbria containing a region of acute focal demyelination induced by in vitro microinjection of lysophosphatidyl chloride (LPC) 6 days earlier, raising bath [Ca2+] to 4.4 mM improved conduction through the damaged area, while lowering it to 0.25 mM depressed conduction. 3. A contrary effect, consistent with the well-known effects of extracellular calcium ion on voltage-sensitive channels, was seen in non-lesioned preparations.

Action Potentials↗