Biomedical subjects

E Shohami

Publications and source records attributed to E Shohami.

At least 73 records · Page 4Linked to original sources

PubMed1996

An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits.

The present study describes the characterization of an experimental model of closed head injury (CHI) in the mouse. This model is a modification of a setup described and used previously in the rat. The weight-drop device was modified and adapted to the size and weight of the mouse and the typical parameters that define the severity of the injury and its outcome were evaluated. The posttraumatic accumulation of water, i.e., cerebral edema, the disruption of the blood-brain barrier (BBB), histopathology, motor and cognitive functions were studied up to 30 days following CHI. Increases in cerebral water content and of BBB permeability were observed in the injured hemisphere at 4 h (p < 0.05) and 24 h (p < 0.01) postinjury, respectively. By 7 days, edema disappeared, while the BBB remained open for up to 30 days. The motor function was evaluated by a set of criteria termed neurological severity score (NSS). NSS was severely impaired immediately after CHI and later showed a spontaneous progressive recovery, although some residual deficits, mainly of beam-walk and balance, were still present at 30 days. Mice trained in the Morris water maze before the injury demonstrated highly significant deficits in memory retention up to at least 11 days postinjury (p < 0.01). Histopathological analysis revealed significant neuronal cell death in CA1, CA2, and CA3 regions of the left hippocampus following CHI. However, in the right hippocampus, overt neuronal cell death was observed only in area CA3 at 7 days after CHI. These results suggest that the modified model of CHI in mice can reproduce the posttraumatic sequelae observed in rats and show that some of the data obtained in this model are essentially similar to those observed in human head injury. The experimental model of CHI in mice may be a useful tool for studies in animals that carry specific genetic alterations, aimed at manipulating neurochemical pathways involved in the pathophysiology of brain damage.

Animals↗

PubMed1996

A novel nonpsychotropic cannabinoid, HU-211, in the treatment of experimental pneumococcal meningitis.

Typical features of pneumococcal meningitis have been demonstrated in rats inoculated with Streptococcus pneumoniae. HU-211, a novel noncompetitive N-methyl-D-aspartate antagonist recently demonstrated to inhibit tumor necrosis factor-alpha production under various conditions, improves recovery in some experimental models of brain injury. The present study tested the efficacy of HU-211 in combination with antimicrobial therapy in reducing brain damage in experimental pneumococcal meningitis. S. pneumoniae-infected rats were treated with saline alone, ceftriaxone alone, or with combination of ceftriaxone and HU-211 18 h after inoculation of the bacteria. Brain edema and blood-brain barrier impairment 48 h after infection were significantly (P<.05) reduced suggest that HU-211 when given concomitantly with antibiotics attenuates brain damage in the rat model of pneumococcal meningitis.

Animals↗

PubMed1996

Inhibition of tumor necrosis factor alpha (TNFalpha) activity in rat brain is associated with cerebroprotection after closed head injury.

We recently demonstrated that closed head injury (CHI) in the rat triggers the production of tumor necrosis factor alpha (TNFalpha) in the contused hemisphere. Other investigations have shown that this cytokine plays a role in the inflammatory response following trauma. The present study was designed to determine whether inhibition of TNFalpha production or activity affects the development of cerebral edema as well as neurological dysfunction and hippocampal cell loss after CHI. To this end, we used two pharmacological agents, each acting via a different mechanism: pentoxifylline (PTX), which attenuates the production of TNFalpha, and tumor necrosis factor binding protein (TBP), a physiological inhibitor of TNFalpha activity. Both agents significantly lessened peak edema formation at 24 h and facilitated the recovery of motor function for < or = 4 days postinjury. In addition, TBP attenuated disruption of the blood-brain barrier and protected hippocampal cells. PTX significantly lowered the brain TNFalpha level (by approximately 80%), and TBP completely abolished the activity of recombinant human TNF when they were added at the same time in the in vitro bioassay. We suggest, therefore, that a decrease in TNFalpha level or the inhibition of its activity is accompanied by reduced brain damage.

Animals↗

PubMed1996

Polyamines induce blood-brain barrier disruption and edema formation in the rat.

Polyamines (PA) are derived from ornithine by the enzyme ornithine decarboxylase (ODC), which is activated very rapidly as acute and delayed responses to brain ischemia and trauma. Polyamines play a role in the disruption of the blood-brain barrier (BBB) in different pathological states. This study examined the effect of exogenous polyamines, administered intracerebrally (i.c.v.) or intracarotidly on BBB function. Putrescine, spermidine and spermine, given individually, were found to disrupt BBB integrity within 15 min of i.c.v. administration (p = 0.03; p = 0.0013; p = 0.042 vs saline treated rats, respectively). The effect was still evident after 1 h; however, since the saline treated rats also showed increased permeability of Evans blue at this time, there was no statistical difference between polyamines or saline treated rats 1 h post injection. When injected into the carotid artery, rapid increase in BBB permeability was found 1 min after putrescine and spermidine (p < 0.01 vs saline), with a slight decline at 15 min. A slower effect was noticed after spermine administration which reached significance only at 15 min. These results suggest a role for PA as mediators of vasogenic edema formation in the brain soon after brain injuries which induce increased production of these compounds.

Analysis of Variance↗

PubMed1996

Effect of magnesium given 1 hour after head trauma on brain edema and neurological outcome.

Excitatory amino acids (EAA), mainly glutamate and aspartate, are released in excessive amounts from terminals of ischemic or traumatically injured neurons. These excessive levels of EAAs initiate a cascade of events believed to lead to secondary delayed damage to the surrounding brain. The N-methyl-D-aspartate receptor antagonists MK-801 and ketamine are reported to suppress excessive EAA release and to attenuate the development of focal brain edema following neuronal injury. Magnesium is also reported to work at the postsynaptic receptor to reduce the neurotoxic effect of glutamate. The present study was undertaken to examine the effect of postinjury treatment with Mg++ on brain edema and neurological outcome after traumatic brain injury. Sixty-nine rats that survived halothane anesthesia and closed head trauma (CHT) were randomly assigned to one of seven experimental groups: sham, CHT, and CHT with administration of Mg++ 1 hour postinjury. At 48 hours, brain tissue Mg++ concentration (calculated from optical density using a standard curve) was significantly increased compared to baseline levels (10.06 +/- 2.44 mg/g vs. 6.83 +/- 0.81 mg/g, p < 0.01 calculated by one-way analysis of variance). Also at 48 hours postinjury, brain tissue specific gravity in the contused hemisphere of Mg(++)-treated rats was significantly greater than that in the contused hemisphere of untreated rats, indicating attenuation of brain edema formation by Mg++. The neurological severity score (NSS) of rats treated with Mg++ improved significantly at both 18 and 48 hours, compared to baseline values obtained 1 hour after CHT but prior to administration of Mg++ (11.2 +/- 2.5 vs. 15.2 +/- 4.1, p = 0.03; and 12.3 +/- 6.1 vs. 17.3 +/- 3.6, p = 0.004, respectively). In the untreated groups, the NSS at 18 and 48 hours was not significantly different from baseline values (that is, no neurological improvement). The present study indicates that postinjury treatment with Mg++ attenuates brain edema formation and improves neurological outcome after experimental CHT.

Animals↗

PubMed1995

45Ca accumulation in rat brain after closed head injury; attenuation by the novel neuroprotective agent HU-211.

45Ca accumulation was studied autoradiographically as a marker for lethally injured brain tissue following closed head injury (CHI), and applied to an investigation of the neuroprotective effect of the non-psychoactive cannabinoid (+)-(3S,4S)-7-hydroxy-D-6 tetrahydro-cannabinol 1,1-dimethylheptyl (HU-211). Amassment of 45Ca in rat brain was examined 24 or 72 h after induction of CHI in the left hemisphere by a weight-drop device. Concentration of 45Ca within 15 different brain regions was assessed by relative optical density. There was increased 45Ca accumulation in the hemisphere ipsilateral to the side of the insult as compared with the contralateral hemisphere. The highest density of radioactive labeling was found in the anterior cortex and in the frontal parts of the parietal cortex, with accumulation expanding as a function of time post injury. On the third day following trauma the amount of accumulated 45Ca was higher than that at 24 h after CHI, with more distant 45Ca-accumulating structures involved: the ventral posterolateral nucleus of the thalamus and the substantia nigra. Histological examination revealed necrotic tissue in the regions accumulating 45Ca. HU-211, a stereoselective inhibitor of the N-methyl-D-aspartate (NMDA) receptor, was injected immediately after induction of trauma. One day after trauma, HU-211 had significantly decreased both the volume of the 45Ca accumulating zone and the concentration of the amassed radioisotope. In the HU-211 treated rats a considerable reduction in radioactive labeling was also found 72 h after trauma. The ability of HU-211 to decrease 45Ca accumulation after head trauma is probably due to its ability to attenuate Ca2+ fluxes through the NMDA receptor-mediated calcium channels and to reduce the depolarization evoked Ca2+ fluxes. On the basis of our results, HU-211 seems to be a promising therapeutic agent for head trauma in humans.

Animals↗

PubMed1995

Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat.

HU-211 is a synthetic, non-psychotropic cannabinoid which acts as a non-competitive NMDA antagonist and antioxidant. We studied the drug's therapeutic window as well as its long-term effect on cognitive and motor functions in a model of closed head injury (CHI) in the rat. A weight-drop device was used to induce CHI in either anesthetized male rats. HU-211 (5 mg/kg) was administered i.v. to the experimental groups. For the therapeutic window study, drug was injected at 4 or 6 h after CHI. Edema (water content) and clinical status (neurological severity score, NSS) were evaluated at 24 h. Reduction of edema was slight, whereas improvement of NSS was significant when the drug was administered at 4 or 6 h (P = 0.0023 and 0.059, respectively). To determine the drug's long-term effect, it was administered 1 h after CHI and additional doses were later given. NSS was evaluated for a period of 30 d. A single dose of HU-211 given 1 h post-CHI improved the clinical outcome during the 30 d period (P < 0.01). Repetitive doses of HU-211 injected during the post traumatic period had similar effects. Cognitive functions were evaluated in the Morris water maze, with rats trained either before or after CHI. CHI resulted in a highly significant impairment of these abilities, whereas HU-211 treatment 1 h after CHI improved performance. Our results indicate that HU-211 is a potent cerebroprotective agent, with a therapeutic window of about 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

The effect of the adrenocortical axis upon recovery from closed head injury.

Fragments and analogs of the hormone ACTH were previously shown to have beneficial effect on the outcome of head injury, while elevated levels of corticosterone (CS) exacerbate it. In the present study we investigated the role of the hypothalamo-pituitary-adrenal (HPA) axis in the pathophysiology of closed head injury (CHI). CHI was produced in ether-anesthetized rats by a calibrated weight-drop device. After evaluating the functional status according to a set of criteria, at 1 and 24 h, the rats were sacrificed and cortical tissue was removed to determine its water content. CHI was also produced in rats that underwent surgical procedures to remove their adrenal gland (ADEX) or the pituitary (HypoX), thus altering the levels of their circulating HPA hormones. Given after CHI, to rats with intact HPA axis, ACTH reduced edema and improved recovery. ADEX rats (6 days postsurgery) had 10-fold higher levels of plasma ACTH. ADEX rats subjected to CHI showed improved functional outcome (p = 0.008) and reduced edema (p = 0.02). We then produced CHI in three groups of rats: HypoX (15 days postsurgery), HypoX treated with ACTH, and controls. In HypoX rats, CHI resulted in increased mortality (35% vs 0) and edema in the surviving rats, and a slower recovery, as compared with the control. Mortality was prevented, edema slightly reduced, and recovery significantly improved after administration of 1-24-ACTH to HypoX rats with CHI. Our results suggest that ACTH has a cerebroprotective effect on the outcome of CHI.

Adrenal Glands↗

PubMed1994

High oligomycin concentrations augment 6-keto-PGF1 alpha production in ventricular cardiomyocytes.

Incubation of cultured ventricular cardiomyocytes with high oligomycin concentrations (100 micrograms/ml), either alone or combined with 2-deoxyglucose (20 mM), led to the rapid depletion of cellular ATP. Inositol (poly)phosphate production decreased, and 6-keto PGF1 alpha production was increased. In cells depleted of ATP, either by low oligomycin concentrations or by sodium azide, 6-keto PGF1 alpha was not appreciably increased. There was a 25% rise in the release of fatty acids from the sn-2 position in glycerophospholipids. We suggest that oligomycin at high concentrations causes the release of free arachidonic acid from phospholipids either by non-PIP2-specific PLC and DG lipase or by phospholipase D, phosphatidic acid phosphatase and DG lipase. The effect is unrelated to decreased cellular ATP content.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Long term exposure to heat reduces edema formation after closed head injury in the rat.

Cerebral edema is one of the major consequences of head trauma (HT); its evolution may cause secondary ischemia and neuronal damage. In a closed head injury model in rats, we have shown BBB disruption and edema formation during the post traumatic period. We have previously shown that chronic exposure to moderate heat improves clinical outcome of rats subjected to HT. Long term exposure to heat results in the achievement of a stable acclimated state, characterized by a lower metabolic rate and improved heat tolerance. In the present study, we investigated the effect of chronic exposure to heat on edema formation after HT. Rats were held at 24 degrees C (CON) or 34 degrees C (ACC) for one month. Injury was then induced under ether anesthesia by a weight drop device. Four or 48 hours later, they were sacrificed for evaluation of BBB integrity (Evans blue, EB, extravasation) or edema formation (specific gravity, SG, or percent water). We found that EB uptake by the contused hemisphere was 6 fold lower in the ACC rats as compared to CON (p < 0.001). Furthermore, edema measured at 48 h by both SG and percent water methods was significantly lower in the acclimated rats (p < 0.01). We suggest that heat acclimation offers protection to rats subjected to head injury, possibly by reduction of plasma proteins extravasation.

Acclimatization↗

PubMed1994

Closed head injury triggers early production of TNF alpha and IL-6 by brain tissue.

In a model of closed head injury (CHI) in the rat we have shown the activation of phospholipase A2 and the production of eicosanoids after injury: at 15 min, mainly 5-hydroxyeicosatetraenoic acid (5-HETE), and at 24 h, mainly prostaglandin E2. The present study was designed to test whether CHI can also trigger the production of cytokines in the brain. CHI was induced in ether-anesthesized rats by a weight-drop device falling over the exposed skull covering the left hemisphere, 1-2 mm lateral to the midline in the midcoronal plane. In the posttraumatic period (1-24 h), the rats were decapitated, cortical tissue from the injured zone of the contused and contralateral hemispheres was removed and sonicated, and cytokine activity was assessed. Whereas no tumor necrosis factor alpha (TNF alpha) activity was found in normal brain tissue, it was detectable in the contused hemisphere (approximately of 72 +/- 50 pg/mg protein) as early as 1 h post-CHI. TNF alpha levels increased at 2 h, peaked at 4 h, (approximately of 609 +/- 540 pg/mg protein), and declined thereafter. At parallel intervals, only low levels of TNF alpha were detected in the contralateral hemisphere. In normal brain, interleukin-6 (IL-6) was nondetectable. Following CHI, high levels of IL-6 were present, although their accumulation lagged behind that of TNF alpha by 2-4 h, peaking at 8 h (62 +/- 31 ng/mg protein). We suggest that the rapid production of TNF alpha and IL-6 following CHI is a local inflammatory response of brain tissue to primary insult.

Animals↗

PubMed1993

Differential effects of phorbol myristate acetate and dexamethasone on protein kinase C activity and eicosanoids production in cultured rat astrocytes.

The effects of phorbol myristate acetate (PMA) and dexamethasone on protein kinase C (PK-C) activity and eicosanoid production were characterized in primary cultures of rat glial cells. PMA (1,000 ng/ml) treatment for 2 hr resulted in a maximal effect (a 4-fold increase in PGE2 production). Longer exposure to PMA (up to 96 hr) resulted in attenuation of PGE2 production. Down-regulation of PK-C activity was assessed in glial cell homogenates under these conditions. Although a 70% inhibition of PK-C activity was measured upon staurosporine treatment, PGE2 production was not affected both under basal conditions and following PMA activation. The production of thromboxane B2 did not change following exposure to PMA. Pretreatment of the cultures with dexamethasone markedly inhibited the PMA-stimulated production of PGE2 but had only a moderate (approximately 26%) inhibitory effect on PGE2 production under basal conditions. Dexamethasone had no effect on basal or PMA-stimulated PK-C activity. Forskolin, which activates adenylate cyclase, did not affect PGE2 production. These data may suggest that activation of PGE2 production by PMA in glial cells is not unequivocally mediated by PK-C activation. The inhibitory effect of dexamethasone on the PMA-stimulated synthesis of PGE2 supports previous findings that glucocorticoids are more effective in inhibiting stimulated rather than basal PGE2 production.

Alkaloids↗

PubMed1993

Cytolysins increase intracellular calcium and induce eicosanoids release by pheochromocytoma PC12 cell cultures.

Cytolysins are the most commonly occurring toxins among bacteria, plants, and animals. By distributing cell membrane, they impair ionic permeability, leading to cell death. In an attempt to investigate cytolysin action on catecholaminergic neurons, we have treated pheochromocytoma cell cultures with Streptolysin S, Staphylococcus aureus alpha and delta, Stoichatus, Parcelsin, and cobra direct lytic factor. To measure neurotoxicity, PC12 cultures were loaded with 51Cr and exposed for 1 hr at 37 degrees C to different concentrations of cytolysins. Cytotoxic dose-response curves have been generated resulting in CD50 (cytotoxic dose 50%) in the range of 1-50 micrograms toxin/culture. Using subcytotoxic concentrations of cytolysins (which are of clinical relevance), changes on intracellular calcium were measured by Fura-2 fluorescence technique. Addition of either Stoichatus toxin and tetanolysin or streptococcus and staphylococcus cytolysins to PC12 cells caused rapidly or gradually a progressive increase in [Ca2+]i, respectively. Under similar conditions, samples of PC12 culture medium were assayed for 3H-arachidonic acid released and by radioimmunoassay for the content of PGE2 (prostaglandin), TXB2 (stable metabolite of thromboxane), and 5-HETE (hydroxy acid lipoxygenase product). PLA2 was activated 4.5-6.0-fold and the levels of all three eicosanoids were increased by 2.5-9-fold (PGE2), 4-6-fold (TXB2), and over 100-fold (5-HETE) by Stoichatus and Parcelsin cytolysins. Upon treatment with Streptolysin S and staphylococcus delta toxins PLA2 (phospholipase A2) was slightly activated (1.5-fold) and the levels of PGE2 and TXB2 increased 1.3-2.0-fold and that of 5-HETE up to 30-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

A tissue culture ischemic device to study eicosanoid release by pheochromocytoma PC12 cultures.

In an attempt to search for neuronal models to investigate the molecular pharmacology of central nervous system ischemia, we have focused on PC12 pheochromocytoma cultures which are now popular in neuroscience research. These chromaffinergic transformed cells, originary from the adrenal medulla, synthesize and release catecholamines and, upon treatment with nerve growth factor (NGF), differentiate to a sympathetic phenotype expressing neurites and excitability. To measure eicosanoid production, undifferentiated or NGF-treated PC12 cultures have been exposed for 1 h to a mixture of N2/CO2 (95:5%), resulting in hypoxia (5 +/- 1% O2), followed by 1 h reoxygenation (21% O2) using a special ischemic device. Hypoxia, up to 2 h, was not followed by significant cytotoxicity or significant production of prostaglandin PGE2. However, upon reoxygenation, a specific release of PGE2 (2-3 fold over control) was measured. A similar PGE2-enhanced release could be induced by 'chemical hypoxia' using 2-deoxyglucose and oligomycin to reduce cellular adenosine triphosphate (ATP). Anoxia (0.1-1% O2, 1 h) achieved by a reduction of culture incubation volume and the reduction in ATP level have been found as critical parameters leading to PC12 cells cytotoxicity. These results emphasize the simplicity and applicability of the tissue culture ischemic device proposed to investigate hypoxia and ischemia at a cellular level.

Adrenal Gland Neoplasms↗

PubMed1993

Interaction between mast cells and glial cells: an in vitro study.

Brain mast cells (MC) are located in close proximity to glial cells and it has been suggested that they belong to the connective tissue phenotype. To determine whether the local microenvironment provided by glial cells can influence mouse bone marrow-derived MC (BMMC), the putative counterpart of mucosal MC, we co-cultured these two cell types. BMMC numbers, morphology, histochemical properties and histamine content as well as glial cell morphology and function were evaluated up to 21 days. Our data indicate that BMMC adhere, proliferate, survive and can be activated to release histamine on the glial cell monolayers without changing their phenotype. Co-cultured glial cells preserve their morphological appearance and function throughout the culture period. These data indicate that central nervous system (CNS) glial cells do not induce phenotypic changes in BMMC and do not interfere with their viability and function.

Animals↗

PubMed1993

A nonpsychotropic cannabinoid, HU-211, has cerebroprotective effects after closed head injury in the rat.

HU-211 is a synthetic, nonpsychotropic cannabinoid, which has been shown to act as a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. The cerebroprotective effects of this compound were assessed in a model of closed head injury in rats. Head trauma (HT) was induced in ether-anesthetized rats by a weight-drop device; recovery was followed up to 48 h. The clinical status of the rats was evaluated at 1, 24, and 48 h after injury, and the extent of edema formation was determined by specific gravity (SG) and water content measurements at 24 or 48 h. The integrity of the blood-brain barrier (BBB) was investigated using Evans-Blue extravasation at 4 h after HT. HU-211 at a dose of 25 mg/kg in middle-chain triglycerides (MCT) oil was given intraperitoneally immediately and 1, 2, or 3 h after impact, and its effect on the various parameters was studied. The drug was found to be very effective in improving motor function recovery. When the drug was given 1 h after HT, the percent of rats able to perform beam walking task on 8.5- and 5-cm wide beams was increased from 30% and 0% to 79% (p = 0.0172) and 57% (p = 0.0029), respectively. The percent of rats able to balance on a 1.5-cm beam for 20 and 40 sec was also significantly increased, from 9% and 0% to 72% (p = 0.0037) and 50% (p = 0.078), respectively. The drug was also effective in reducing the BBB breakdown by more than four fold, as compared with control (548 +/- 94 versus 128 +/- 19 ng Evans blue/g tissue; p < 0.05) and attenuating cerebral edema. SG was 1.0367 +/- 0.0007 versus 1.0399 +/- 0.0005, and percent water content was 83.06 +/- 0.57 versus 80.78 +/- 0.36 (p < 0.05) in control and HU-211 treated rats, respectively. Similar significant protection was found when the drug was injected 2 h after the injury; however, at 3 h the effect was somewhat less pronounced. We suggest that this novel drug is a potential cerebroprotector in head trauma with a therapeutic window of at least 2 to 3 h.

Animals↗

PubMed1993

Role of glucocorticoids in the regulation of brain prostaglandin biosynthesis under basal conditions and in response to endotoxin.

Glucocorticoids (GC) are known to inhibit eicosanoid production in various peripheral tissues; however, their role in the regulation of basal and induced prostaglandin (PG) biosynthesis in the brain is still not clear. In the present study we examined the effect of exogenous dexamethasone (dex) or endogenous GC on basal and on bacterial endotoxin (lipopolysaccharide, LPS) induced ex vivo production of PGE2 by the frontal cortex of rat brain. The experimental groups were: 1) intact rats; 2) rats in whom endogenous GC were removed either by surgical or by chemical (metopirone) adrenalectomy (adex); and 3) rats exposed to specific corticosteroid receptor antagonists. In intact rats, the basal rate of PGE2 ex vivo synthesis was about 120 pg/mg protein.hr; dex (0.05-0.5 mg/100 g body wt ip) did not affect this level. Exposure to LPS (50 micrograms, intracerebroventricular) induced a 2-fold increase in PGE2, whereas pretreatment with dex abolished this increase. Bilateral adex or metopirone alone did not change PGE2 synthesis, whereas LPS administration to surgical or chemical adex rats resulted in a 4-fold increase in PGE2 production. Administration (intracerebroventricular) of either one or both of the specific corticosteroid receptor antagonists, RU-28318 (type I) and RU-38486 (type II) did not affect basal PGE2 production. When LPS was given after either one of these antagonists, a slight but significant elevation of PGE2 occurred, as compared to LPS-treated controls. When both antagonists were coadministered, the LPS-induced production of PGE2 was much more pronounced, similar to levels of LPS-treated, adex rats. These results suggest that LPS-induced production of PGE2, but not the basal production, is regulated by either endogenous or exogenous GC, and the inhibitory effect of GC on brain PG synthesis is mediated via both type I and II corticosteroid receptors.

Adrenalectomy↗

PubMed1993

Blood-brain barrier permeability, cerebral edema, and neurologic function after closed head injury in rats.

We previously described the time course of changes in neurologic status (as indicated by neurologic severity score [NSS]) and cerebral edema (as indicated by brain tissue specific gravity and water content) after closed head trauma in rats. The present study was designed to determine whether head trauma alters the integrity of the blood-brain barrier (BBB), the role of the BBB in edema formation and neurologic outcome, and the effect of MK-801 (a noncompetitive N-methyl-D-aspartate receptor antagonist) on BBB permeability. Rats in which cranial impact was delivered during ether anesthesia (n = 106) were killed at 15 min, 1, 2, 4, 10, and 24 h, and 2, 4, and 7 days. Control rats (n = 12) received no cranial impact. Subsets of head-injured rats killed at 4 and 24 h received MK-801 (3 mg/kg intraperitoneally) 1 h after injury. BBB permeability was assessed with intravenous injection of Evans Blue dye, cerebral edema was assessed by determining brain tissue specific gravity and water content, and neurologic status was assessed using NSS. Tissue extravasation of Evans Blue was maximal in the injured hemisphere 4 h after injury, but a residual BBB permeability defect was still evident as long as 4 days after the insult. In MK-801-treated rats, extravasation of Evans Blue in the injured hemisphere was not significantly different from that in the noninjured hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗