Difference In Brain Water Content Research Articles

Controlled Decompression Attenuates Brain Injury in a Novel Rabbit Model of Acute Intracranial Hypertension.

BackgroundIn the past, standard rapid decompressive craniectomy was used to alleviate the secondary damage caused by high intracranial pressure. Recent clinical studies showed that controlled decompression may have a better curative effect than rapid decompression. However, the effect on controlled decompression in animals is unclear.Material/MethodsTotally 80 healthy male New Zealand rabbits were randomly divided into a sham group (n=20), a rapid decompression group (n=30), and a controlled decompression group (n=30). An intracranial hypertension model was induced by injecting saline into an epidural balloon catheter and reducing ICP slowly and gradually by use of a pressure pump. The model was evaluated and analyzed by general observations, imaging examination, ICP values, behavioral score, brain water content, Nissl staining, and caspase-3 protein detection.ResultsThe mortality rate was 36.7% (11/30) in the rapid group, 20% (6/30) in the controlled group, and 5% (1/20) in the sham group. The incidence of epidural hematoma in the controlled group was lower than in the rapid group (p<0.01). The ICP was significantly lower in the controlled group than in the rapid group (p<0.001), and the behavioral score in the rapid group was higher than in the controlled group (p<0.05). There was a marked difference in brain water content between the controlled group and the rapid group (p<0.01). Nissl staining demonstrated that the ratio of Nissl body in the controlled group was significantly higher than in the rapid group (p<0.01). WB detection showed the expression of Caspase-3 in the controlled group was lower than in the rapid group (p<0.05).ConclusionsThe results show the advantages of use of controlled decompression with intracranial hypertension. The animal model we developed provides a platform for further research on controlled decompression.

Perinatal Micro-Bleeds and Neuroinflammation in E19 Rat Fetuses Exposed to Utero-Placental Ischemia.

Offspring of preeclampsia patients have an increased risk of developing neurological deficits and cognitive impairment. While low placental perfusion, common in preeclampsia and growth restriction, has been linked to neurological deficits, a causative link is not fully established. The goal of this study was to test the hypothesis that placental ischemia induces neuroinflammation and micro-hemorrhages in utero. Timed-pregnant Sprague Dawley rats were weight-matched for sham surgery (abdominal incision only) or induced placental ischemia (surgical reduction of utero-placental perfusion (RUPP)); n = 5/group on gestational day 14. Fetal brains (n = 1–2/dam/endpoint) were collected at embryonic day (E19). Placental ischemia resulted in fewer live fetuses, increased fetal demise, increased hematocrit, and no difference in brain water content in exposed fetuses. Additionally, increased cerebral micro-bleeds (identified with H&E staining), pro-inflammatory cytokines: IL-1β, IL-6, and IL-18, eotaxin (CCL11), LIX (CXCL5), and MIP-2 (CXCL2) were observed in RUPP-exposed fetuses. Microglial density in the sub-ventricular zone decreased in RUPP-exposed fetuses, with no change in cortical thickness. Our findings support the hypothesis that exposure to placental ischemia contributes to microvascular dysfunction (increased micro-bleeds), fetal brain inflammation, and reduced microglial density in proliferative brain areas. Future studies will determine whether in utero abnormalities contribute to long-term behavioral deficits in preeclampsia offspring through impaired neurogenesis regulation.

The Relationship Between the Expression of Serum S100A8/A9 and the Degree of Brain Injury in Rats After Cardiopulmonary Resuscitation

This study is to investigate the expression of serum S100A8/A9 in rats after cardiopulmonary resuscitation (CPR) and its correlation with brain injury after CPR. Thirty-six male SD rats were randomly divided into control group (n = 6), cardiopulmonary resuscitation group (n = 24) and sham operation group (n = 6). The cardiopulmonary resuscitation group was further divided into four subgroups according to the time after recovery of autonomous circulation: 6-hour group, 12-hour group, 24-hour group and 48-hour group, with 6 rats in each group. The rats in the cardiopulmonary resuscitation group was conducted by asphyxia then given cardiopulmonary resuscitation (CPR), while the rats in the sham operation group were given tracheal intubation without asphyxia. The rats in each group were assessed by modified Neurological Severity Score (mNSS). The vein blood from tail was collected to detect the expression of serum S100A8/A9. Then the brain tissue was taken to measure the water content. Our results showed that the neurological function of the sham-operated group and the control group was normal, the mNSS scores of which were 0. However, the neurological function score in the CPR group decreased gradually with time, but it was still significantly higher than that in the normal value until 48 hours (P &lt; 0.05). There was no significant difference in brain water content between the sham-operated group and the control group (P &gt; 0.05). The water content of brain tissue in sham-operated group was higher than that in control group at 6 h, and the amount was increasing as the time extended. The level reached the highest at 24 h and started to decrease at 48 h, but the it was still higher than that in sham-operated group (P &lt; 0.05). The expression level of serum S100 A8/A9 in sham-operated group was slightly higher than that in control group, but there was no statistical difference (P &gt; 0.05); The expression level of S100 A8/A9 in cardiopulmonary resuscitation group was significantly higher than that in control group at 6 h, and still increased at 24 h. Although the level decreased at 48 h, but was still higher than that in sham operation group (P &lt; 0.05). The mNSS score and brain water content were significantly positively correlated with serum S100 A8/A9 (r = 0.48, P &lt; 0.001; r = 0.63, P &lt; 0.001). In conclusion, the level of serum S100A8/A9 in rats after cardiopulmonary resuscitation is significantly increased, which is positively correlated with the degree of brain injury in rats.

Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat.

Traumatic brain injury causes a disruption of the vascular endothelial glycocalyx layer that is associated with an overactivation of the sympathoadrenal system. We hypothesized that early and unselective beta-blockade with propranolol alone or in combination with the alfa2-agonist clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma. We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal motor function. We found no difference in brain water content (mean ± SD) between propranolol (80.8 ± 0.3%; 95% confidence interval [CI], 80.7-81.0) and vehicle (81.1 ± 0.6%; 95% CI, 80.8-81.4) (p = 0.668) or between propranolol/clonidine (80.8 ± 0.3%; 95% CI, 80.7-81.0) and vehicle (p = 0.555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels. This study does not provide any support for unselective beta-blockade with propranolol or the combination of propranolol and the alfa2-agonist clonidine on brain water content. The novel finding of an increase in plasma concentrations of epinephrine and syndecan-1 after propranolol treatment in traumatic brain injury is of unclear significance and should be investigated further.

Efficiency of integrin αvβ3 inhibitor Cilengitide in acute cerebral ischemia in rats

To explore the effect of the integrin αvβ3 inhibitor Cilengitide on the blood brain barrier (BBB) permeability, brain edema, neuronal cell apoptosis and the relation with the vascular endothelial growth factor (VEGF)expression in acute cerebral ischemia rats. A rat focal cerebral ischemia/reperfusion model was established by middle cerebral artery occlusion. Rats with middle cerebral artery occlusion, in accordance with the random number table, were divided into four groups: (1) the rats in Cilengitide group A (n=30) were treated with Cilengitide at a dose of 100 μg/kg; (2) the rats in Cilengitide group B (n=28) were treated with Cilengitide at a dose of 200 μg/kg; (3) the rats in sham group (n=31), without inserting thread into middle cerebral artery, were treated with normal saline; (4) the rats in control group (n=27) were treated with normal saline.All rats were treated with Cilengitide or saline 1 hour after infarction, given reperfusion 2 hours after infarction and were sacrificed 22 hours after reperfusion.The brain-water content was measured by dry/wet weight method. The permeability of BBB was measured by quantifying Evans Blue. The infarction volume was measured by 2, 3, 5-tripheyl tetrazolium Chloride (TTC) staining. Expression level of VEGF, P-Flk, Cleaved-Caspase-3 was measured by immunohistochemistry and Western blot, respectively.The neuronal cell apoptosis was evaluated by terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL). Compared with Control group, treatment groups with cilengitide at the dose of 100 μg/kg and 200 μg/kg reduced brain-water content [(80.8±1.1)% vs (84.8±1.4)%, (81.0±1.4)% vs (84.8±1.4)%, P<0.05], reduced exudation of Evans blue[(9.2±1.1) μg/g vs (12.2±0.8) μg/g, (8.6±0.6) μg/g vs (12.2±0.8) g/g, P<0.05], reduced infarction volume[(31.9±4.9) mm(3) vs(43.0±2.2) mm(3), (29.2±3.5) mm(3) vs(43.0±2.2) mm(3), P<0.05] , reduced neuronal cell apoptosis [(36±4)vs(69±6)、(35±3)vs (69±6), P<0.05]. Compared with sham group, Cilengitide group A and Cilengitide group B had lower brain-water content, permeability of BBB, infarction volume, expression level of VEGF, P-Flk, Cleaved-Caspase-3 and neuronal cell apoptosis (P<0.05). When Cilengitide group A was compared with Cilengitide group B, there were no significant differences in brain-water content, permeability of BBB, infarction volume, expression level of VEGF, P-Flk, Cleaved-Caspase-3 and neuronal cell apoptosis (P>0.05). The integrin αvβ3 inhibitor Cilengitide improves outcomes in the MCAO model by preserving the blood-brain barrier, attenuating brain edema and inhibiting neuronal cell apoptosis, which may occur in a VEGF-and VEGF-receptor-dependent manner, with the same efficacy between Cilengitide 100 μg/kg and 200 μg/kg after 23 hours treatment.

Effects and its mechanisms of hypertonic saline hydroxyethyl starch 200/0.5 solution in rats with ischemic cerebral edema

Objective To investigate effects and its mechanisms of hypertonic saline hydroxyethyl starch 200/0.5 solution on intracranial pressure and brain water content in rats with ischemic cerebral edema. Methods All experiments were conducted in the animal experimental center of Sun Yat-sen University. The 28 male Sprague-Dawle (SD) rats were randomly (random number) divided into hypertonic saline hydroxyethyl starch group, hydroxyethyl starch group, control group and sham operation group, each n =7. Ischemic cerebral edema model was reproduced by middle cerebral artery occlusion(MCAO) , followed by reperfusion after ischemia for 2 hours (If the moldel was not successful, other rats were operated to fill the missing models) . Then reperfusion after ischemia 2 hours and received hypertonic saline hydroxyethyl starch and hydroxyethyl starch via tail vein at the beginning of reperfusion. The colloidal osmotic pressure (COP) and intracranial pressure (ICP) were evaluated on 0, 2, 6, 12, 18, 24 hours after the surgery. The water content of the right hemisphere was measured on 24 h after the surgery. Results The ICP of hypertonic saline hydroxyethyl starch group, hydroxyethyl starch group and control group were significantly higher than that of sham operation group on 2, 6, 12, 18, 24 h after the surgery. The ICP of hypertonic saline hydroxyethyl starch group was significantly lower than those of hydroxyethyl starch group and control group on 2, 6, 12, 18 and 24 h. But there was no significant difference in ICP of the hydroxyethyl starch group compared with that of control group at all time points. The COP of hypertonic saline hydroxyethyl starch group and hydroxyethyl starch group were significantly higher than the control group and sham operation group at each time point; There was no significant difference in COP (mmHg) of the hydroxyethyl starch group compared with that of hypertonic saline hydroxyethyl starch group at all time points. The brain water content (BWC) of hypertonic saline hydroxyethyl starch group, hydroxyethyl starch group and control group were significantly higher than that of sham operation group on 24 hours after the surgery [(81.24±0.36)%, (83.04±0.10)%, (83.14±0.41)% vs. (78.37±0.37)%, all P = 0.000], BWC of hypertonic saline hydroxyethyl starch group lower than these of hydroxyethyl starch group [(81.24 ±0.36)% vs. (83.04 ±0.10) %, P =0.000] and control group [(81.24 ±0.36)% vs. (83.14 ±0.41) %, P =0.000]. There was no significant difference in BWC of the hydroxyethyl starch group compared with that of control group [(83.04 ± 0.10)% vs. (83.14 ± 0.41) %, P =0.578]. Conclusion Hypertonic saline hydroxyethyl starch solution could significantly ameliorate ischemic cerebral edema and reduce ICP, but the relationship between its elevated COP and reduced ICP has not been confirmed. Key words: Hypertonic saline hydroxyethyl starch solution; Cerebral ischemia/reperfusion injury; Colloidal osmotic pressure; Intracranial pressure; Cerebral edema

Effect of Dexmedetomidine on Brain Edema and Neurological Outcomes in Surgical Brain Injury in Rats

Surgical brain injury (SBI) is damage to functional brain tissue resulting from neurosurgical manipulations such as sharp dissection, electrocautery, retraction, and direct applied pressure. Brain edema is the major contributor to morbidity with inflammation, necrosis, oxidative stress, and apoptosis likely playing smaller roles. Effective therapies for SBI may improve neurological outcomes and postoperative morbidities associated with brain surgery. Previous studies show an adrenergic correlation to blood-brain barrier control. The α-2 receptor agonist dexmedetomidine (DEX) has been shown to improve neurological outcomes in stroke models. We hypothesized that DEX may reduce brain edema and improve neurological outcomes in a rat model of SBI. Male Sprague-Dawley rats (n = 63) weighing 280 to 350 g were randomly assigned to 1 of 4 IP treatment groups: sham IP, vehicle IP, DEX 10 mg/kg, and DEX 30 mg/kg. Treatments were given 30 min before SBI. These treatment groups were repeated to observe the physiologic impact of DEX on mean arterial blood pressure (MAP), heart rate (HR), and blood glucose on SBI naïve animals. Rats were also assigned to 4 postinjury IV treatment groups: sham IV, vehicle IV, DEX 10/5, and DEX 30/15 (DEX group doses were 10 and 30 mg/kg/hr, with 5 and 15 mg/kg initial loading doses, respectively). Initial loading doses began 20 min after SBI, followed by 2 h of infusion. SBI animals were subjected to neurological testing 24 h after brain injury by a blinded observer, promptly killed, and brain water content measured via the dry/wet weight method. All treatment groups showed a significant difference in ipsilateral frontal brain water content and neurological scores when compared with sham animals. However, there was no difference between DEX-treated and vehicle animals. Physiologic monitoring showed treatment with low or high doses of DEX significantly decreased MAP and HR, and briefly increased blood glucose compared with naïve or vehicle-treated animals. DEX administration did not reduce brain edema or improve neurological function after SBI in this study. The statistical difference in brain water content and neurological scores when comparing sham treatment to vehicle and DEX treatments shows consistent reproduction of this model. Significant changes in MAP, HR, and blood glucose after DEX as compared to vehicle and sham treatments suggest appropriate delivery of drug.

Sampling of CSF via the Cisterna Magna and Blood Collection via the Heart Affects Brain Water Content in a Rat SAH Model

The aim of this study was to evaluate whether sampling of cerebrospinal fluid (CSF) via the cisterna magna and of blood via the heart affects brain water content in a rat subarachnoid hemorrhage (SAH) model. Twenty-nine animals were divided into four groups: sham-operated group with sampling of CSF and blood (Sham S+), sham-operated group without sampling of CSF and blood (Sham S-), SAH group with sampling of CSF and blood (SAH S+), and SAH without sampling of CSF and blood (SAH S-). SAH was induced via endovascular perforation of the left internal carotid artery bifurcation. Cerebrospinal fluid via the cisterna magna and blood via cardiac puncture was collected in the Sham S+ and SAH S+ groups before killing the animals for brain water content measurements. Left hemisphere brain water content was significantly higher in the SAH S- group compared with the Sham S- group (p< 0.05) and in Sham S+ group compared with the Sham S- group (p<0.05). There was no significant difference in brain water content of the left hemisphere between the SAH S+ and Sham S+ groups (p=NS). There was no significant difference in brain water content in other parts of brains. Sampling of CSF and blood affected brain water content in Sham animals and therefore it is not accurate to use these values from Sham animals for comparison with SAH animals.

Effects of different degrees of acute normovolemic hemodtiution on serum S-100B protein concentration and cerebral oxygen metabolism in rabbits

Objective To investigate the effects of different degrees of acute normovolemic hemodilution (ANH) with 6% HES 20010.5 on serum S-100B protein concentration and cerebral oxygen metabolism at 37℃ in rabbits.Methods Thirty-two adult rabbits weighing 2.0-2.5 kg were randomly assigned into 4 groups (n = 8each) : Ⅰ control group underwent no ANH and Ⅱ , Ⅲ , Ⅳ ANH group underwent ANH with hematocrit (Hct)reduced to 24%, 18% and 12% respectively. The animals were anesthetized with iv 20% urethane 5 ml/kg,tracheostomized and mechanically ventilated (VT = 15 ml/kg, RR = 30 bpm). The body temperature was maintained at 37℃. Left carotid artery and jugular vein were cannulated for BP monitoring, blood gas analysis and blood sampling. Right jugular vein was cannulated for CVP monitoring. Left femoral artery and vein were cannulated for hemodilution. Blood withdrawn from femoral artery was simultaneously replaced by iv infusion of equal volume of HES (200/0.5) until the target Hct was achieved. Hemodynamics parameters, were recorded and blood gases were analyzed and serum S-100B protein concentration and cerebral O2 metabolic rate (CERO2) were determined before (baseline) and at 2, 4 and 8 h after ANH. Brain water content was measured by wet/dry brain weight ratio. Results There were no significant differences in serum S-100B protein concentration, CERO2 and pH value between group Ⅰ and group Ⅱ (Hct 24%). Serum S-100B protein concentration and CERO2 were significantly increased at 8 h after ANH as compared with the baseline before ANH in group Ⅰ (Her 18%). Serun S-100B protein concentration and CERO2 were significantly increased at 2, 4 and 8 h after ANH as compared with the baseline before ANH in group Ⅳ (Hct 12%). There was no significant difference in brain water content among the 4 groups. Conclusion ANH does not affect cerebral O2 metabolic when Hct is reduced to 24%. CERO2 can not be sustained and ischemic cerebral injury may occur when Hct is reduced to≤18%. Key words: Hemodilution ; S100 proteins; Brain ; Oxygen consumption

LPS-induced endotoxic shock does not cause early brain edema formation – An MRI study in rats

Early microcirculatory failure is assumed as a key factor in the development of a septic encephalopathy. However, brain edema is also a common finding in sepsis syndromes possibly interfering with the vasoregulative mechanisms of the brain. We assessed the occurrence of brain edema in a rat model of endotoxic shock. Eleven mechanically ventilated male CD-rats. Intravenous application of 5 mg/kg LPS (n = 8) or vehicle (n = 3). Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on cerebral MRI at baseline and repeatedly for up to 3.5 h after LPS-injection. Change in blood pressure was compensated with norepinephrine. Brain water content was quantified using the wet/dry method. All LPS-treated rats developed endotoxic shock. No significant difference in T2RT or ADC was detectable before and after LPS-injection (T2RT: baseline 60.33 +/- 1.21; after 3.5 h 60.15 +/- 0.59; ADC: baseline 6.86 +/- 0.51; after 3.5 h 6.75 +/- 0.33). Post-mortem analysis did not indicate a difference in brain water content between septic and non-septic animals. Reports of early microcirculatory failure seem not to be related to the occurrence of early (< or =3.5 h) brain edema.

Effects of transient cerebral ischemia and reperfusion injury on expression of aquaporin-4 and apoptosis in hippocampal neurons of aged animals: experiment with rats

To investigate the effects of transient cerebral ischemia and reperfusion injury on brain edema and apoptosis hippocampal neurons of aged animals. 120 19-21-month-old healthy Wistar rats underwent four-vessel occlusion to establish whole cerebral ischemia model and were randomly divided into 3 equal groups to undergo ischemia for 1 min, 3 min, and 5 min respectively. Every group was re-divided into 5 equal sub-groups to undergo reperfusion for 12 h, 1 d, 2 d, 3 d, and 7 d respectively. Another 40 rats underwent sham operation to be used as controls. At different reperfusion time points 4 rats from each subgroup were killed to measure the wet and dry weights of the hippocampus. The brains of the remaining 4 rats from each subgroup underwent HE staining and microscopy. The expression of aquaporin-4 (AQP4) was detected by SABC immunohistochemical technique, and the neuron apoptosis in hippocampus was detected by TUNEL method. There was no significant differences in brain water content and expression of AQP4 between the ischemia 1 min and 3 min subgroups and the corresponding sham-operation subgroups (all P > 0.05), however, the brain water contents and AQP4 expression levels of the ischemia 5 min subgroups were all significantly higher than those of the corresponding sham-operation subgroups (all P < 0.05). There were only a few TUNEL-positive cells in the sham-operation subgroups and ischemia 1 min subgroups, however, the numbers of TUNEL-positive cells of the ischemia 3 min and 5 min subgroups were all significantly higher. The number of TUNEL-positive cells raised 12 h after ischemia, peaked 1 day after, and began to go down 3 days later. The aged animals are more sensitive to cerebral ischemia/reperfusion injury, and transient cerebral ischemia may cause brain edema, and increase of apoptotic cells and AQP4 expression. Neuron apoptosis is more sensitive to cerebral ischemia than brain edema and AQP4 expression. After reperfusion neuron apoptosis peaks earlier and lasts longer in the aged animals.

Basic fibroblast growth factor alleviates brain injury following global ischemia reperfusion in rabbits

The aim of this study was to explore the protective effect of basic fibroblast growth factor (bFGF) on brain injury following global ischemia reperfusion and its mechanisms. Brain injury following global ischemia was induced by four vessels occlusion and systemic hypotension. Twenty-four rabbits were randomized into three groups: group A, only dissection of vessels; group B, intravenous infusion of normal saline after reperfusion for 6 h; group C, 30 microg/kg bFGF injected intravenously at the onset of reperfusion, then infused with 10 microg/(kg.h) for 6 h. Serum neuron specific enolase (NSE), S-100B, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-8 (IL-8) were measured before ischemia, 30 min after ischemia, 0.5, 1, 3, 6 h after reperfusion. Brain water content was determined and cerebral histopathological damages were compared. NSE and S-100B were increased 1 h after reperfusion and reached their peaks 6 h after reperfusion, but were much higher in group B than those in group C 3, 6 h after reperfusion. In groups B and C, TNF-alpha was increased after ischemia and IL-1 and IL-8 were increased significantly 0.5 h after reperfusion, then reached their peaks 6 h, 3 h, 6 h after reperfusion respectively. TNF-alpha and IL-8 at the time points of 1 h and 3 h and IL-1 at 3 h and 6 h in group C were correspondingly lower than those in group B. These indices in group A were nearly unchanged. There were less severe cerebral histopathological damages in group C compared with group B, but no difference in brain water content. It could be concluded that bFGF alleviates brain injury following global ischemia and reperfusion by down-regulating expression of inflammatory factors and inhibiting their activities.

Effects of mexiletine, ginkgo biloba extract (EGb 761), and their combination on experimental head injury.

Lipid peroxidation (LP) and brain edema are important factors that produce tissue damage in head injury. The purpose of this study was to investigate the effect of mexiletine, gingko biloba extract (EGb 761), and their combination on LP and edema after moderate head trauma. Forty rats were randomly and blindly divided into four groups of ten animals each: control group (bolus injection of physiological saline), mexiletine group (50 mg/kg per injection), EGb 761 group (30 mg/kg per injection), and mexiletine plus EGb 761 group (50 mg/kg and 30 mg/kg per injection, respectively). The injections were given intraperitoneally at 1 h, 9 h, and 17 h after trauma. Twenty-four hours after injury, the rats were killed, and malondialdehyde (MDA) levels and brain water content were determined. Rats treated with mexiletine, EGb 761, and mexiletine plus EGb 761 had significantly lower MDA levels than the control group (P<0.01). The lowest MDA levels were measured in the mexiletine plus EGb 761 group. However, there was no significant difference in brain water content between treated groups and the control group (P>0.05). These findings show the usefulness of mexiletine and its combination with EGb 761 as a cerebroprotective agent in this model of experimental head injury.

Effect of a prostacyclin derivative (OP-41483) and a hyperosmotic agent (glycerol) on brain edema and metabolism in cerebral ischemia.

A PGI2 derivative, OP-41483, and a hyperosmotic agent, glycerol, were tested for possible beneficial effects on brain edema, metabolism and pathological changes in cerebral ischemia. Combination treatment with these agents was also tested. Cerebral ischemia was produced in spontaneously hypertensive rats, using bilateral common carotid artery ligation (BLCL). OP-41483 was administered four times, hourly (500 ng/kg x 4, i.p.). Ten percent glycerol was administered intravenously (6.6 ml/kg). And, for the combination treatment, OP-41483 was administered three times, hourly (500 ng/kg x 3, i.p.), and 10% glycerol was administered intravenously (6.6 ml/kg) in the same manner as the glycerol treated group. In ischemic controls, saline was administered intravenously (6.6 ml/kg). After 3 h of ischemia, brain water content and metabolites were determined and pathological observation was conducted using electron microscopy. OP-41483 treated animals maintained higher levels of ATP concentration and reduced accumulation of lactate, but showed no difference in brain water content compared to saline treated controls. Glycerol treated animals showed significance in terms of reduction of brain water content and accumulation of lactate. Glycerol abated the depletion of ATP concentration. OP-41483+glycerol treated animals showed the most significant effect on the reduction of brain water content and accumulation of lactate. The combination treatment also maintained higher levels of ATP concentration. Additionally, swelling of astrocytic foot processes and mitochondria with destroyed crista were not observed pathologically in the combination treated animals. These results show that OP-41483, glycerol and combination treatment are beneficial in the treatment of cerebral ischemia. They also indicate that the combination treatment significantly enhances the protective effects compared to individual treatment.