Effect of hypothermia on brain edema formation following intracerebral hemorrhage in rats

Object Preconditioning with hyperbaric oxygen (HBO2) reduces ischemic brain damage. Activation of p44/42 mitogen-activated protein kinases (p44/42 MAPK) has been associated with preconditioning-induced brain ischemic tolerance. This study investigated if preconditioning with HBO2 protects against intracerebral hemorrhage (ICH)–induced brain edema formation and examined the role of p44/42 MAPK in such protection. Methods The study had three experimental groups. In Group 1, Sprague-Dawley rats received two, three, or five consecutive sessions of preconditioning with HBO2 (3 ata, 100% xygen, 1 hour daily). Twenty-four hours after preconditioning with HBO2, rats received an infusion of autologous blood into the caudate. They were killed 1 or 3 days later for brain edema measurement. Rats in Group 2 received either five sessions of preconditioning with HBO2 or control pretreatment and were killed 24 hours later for Western blot and immunohistochemical analyses. In Group 3, rats received an intracau-date injection of PD098059 (an inhibitor of p44/42 MAPK activation) before the first of five sessions of preconditioning with HBO2. Twenty-four hours after the final preconditioning with HBO2, rats received an intracaudate blood infusion. Brain water content was measured 24 hours after ICH. Results Fewer than five sessions of preconditioning with HBO2 did not significantly attenuate brain edema after ICH. Five sessions of preconditioning with HBO2 reduced perihematomal edema 24 and 72 hours after ICH (p < 0.05). Strong p44/42 MAPK immunoreactivity was detected in the basal ganglia 24 hours after preconditioning with BO2. Intracaudate infusion of PD098059 abolished HBO2preconditioning–induced protection against ICH-induced brain edema formation. Conclusions Preconditioning with HBO2 protects against brain edema formation following ICH. Activation of the p44/42 MAPK pathway contributes to that protection. Preconditioning with HBO2 may be a way of limiting brain injury during invasive neurosurgical procedures that cause bleeding.

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Seizures induced by intracerebral injection of thrombin: a model of intracerebral hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.1997.87.1.0073 ◽

1997 ◽

Vol 87 (1) ◽

pp. 73-78 ◽

Cited By ~ 72

Author(s):

Kevin R. Lee ◽

Ivo Drury ◽

Elizabeth Vitarbo ◽

Julian T. Hoff

Keyword(s):

Intracerebral Hemorrhage ◽

Electrical Activity ◽

Brain Edema ◽

Seizure Activity ◽

Neurological Deficits ◽

Coagulation Cascade ◽

Thrombin Inhibitor ◽

Eeg Monitoring ◽

Edema Formation ◽

Brain Edema Formation

✓ The coagulation cascade plays an important role in brain edema formation caused by intracerebral blood. In particular, thrombin produces brain injury via direct brain cell toxicity. Seizures and increased cerebral electrical activity are commonly associated with intracerebral blood and are possible effects of thrombin leading to cell injury in the brain. In this study, artificial clots containing concentrations of thrombin found in hematomas were infused intracerebrally in rats. The animals were observed clinically for seizure activity, behavior, and neurological deficits. Several animals underwent video electroencephalographic (EEG) monitoring during intracerebral infusion and for 30 minutes postinfusion. All animals were killed 24 hours after injection, and brain water and ion contents were measured to determine the amount of brain edema. Clinically, thrombin produced focal motor seizures in all animals. None of the control animals or those receiving Nα-(2-Naphthalenesulfonyl-glycyl)-4-amidino-DL-phenylalanine-piperidide (α-NAPAP), a thrombin inhibitor added to the thrombin, showed clinical evidence of seizures. Of the rats undergoing EEG monitoring, all animals receiving thrombin showed electrical evidence of seizure activity, whereas none of the control animals exhibited seizure activity. There was no evidence of seizure activity on EEG monitoring when α-NAPAP was injected along with the thrombin. In addition, the artificial clots containing thrombin produced agitation and a circling tendency in the rats, along with brain edema. These results indicate that the coagulation cascade is involved in seizure production and increased brain electrical activity, which contribute to the neurological deficits and brain edema formation that are seen with intracerebral hemorrhage.

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Effects of Brain Hypothermia on Brain Edema Formation After Intracerebral Hemorrhage in Rats

Hypothermia for Acute Brain Damage ◽

10.1007/978-4-431-53961-2_4 ◽

2004 ◽

pp. 29-35 ◽

Cited By ~ 1

Author(s):

Nobuyuki Kawai ◽

Masahiko Kawanishi ◽

Masanobu Okauchi ◽

Seigo Nagao

Keyword(s):

Intracerebral Hemorrhage ◽

Brain Edema ◽

Edema Formation ◽

Brain Edema Formation

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Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats

Journal of Neurosurgery ◽

10.3171/jns.1998.89.6.0991 ◽

1998 ◽

Vol 89 (6) ◽

pp. 991-996 ◽

Cited By ~ 236

Author(s):

Guohua Xi ◽

Richard F. Keep ◽

Julian T. Hoff

Keyword(s):

Intracerebral Hemorrhage ◽

Brain Edema ◽

Sprague Dawley ◽

Edema Formation ◽

Content Type ◽

Packed Red Blood Cells ◽

Brain Water ◽

Packed Rbcs ◽

Brain Edema Formation ◽

Fine Print

Object. The mechanisms of brain edema formation following spontaneous intracerebral hemorrhage (ICH) are not well understood. In previous studies, no significant edema formation has been found 24 hours after infusion of packed red blood cells (RBCs) into the brain of a rat or pig; however, there is evidence that hemoglobin can be neurotoxic. In this study, the authors reexamined the role of RBCs and hemoglobin in edema formation after ICH. Methods. The experiments involved infusion of whole blood, packed RBCs, lysed RBCs, rat hemoglobin, or thrombin into the right basal ganglia of Sprague—Dawley rats. The animals were killed at different time points and brain water and ion contents were measured. The results showed that lysed autologous erythrocytes, but not packed erythrocytes, produced marked brain edema 24 hours after infusion and that this edema formation could be mimicked by hemoglobin infusion. Although infusion of packed RBCs did not produce dramatic brain edema during the first 2 days, it did induce a marked increase in brain water content 3 days postinfusion. Edema formation following thrombin infusion peaked at 24 to 48 hours. This is earlier than the peak in edema formation that follows ICH, suggesting that there is a delayed, nonthrombin-mediated, edemogenic component of ICH. Conclusions. These results demonstrate that RBCs play a potentially important role in delayed edema development after ICH and that RBC lysis and hemoglobin toxicity may be useful targets for therapeutic intervention.

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