Complement activation in the brain after experimental intracerebral hemorrhage

2000 ◽  
Vol 92 (6) ◽  
pp. 1016-1022 ◽  
Author(s):  
Ya Hua ◽  
Guohua Xi ◽  
Richard F. Keep ◽  
Julian T. Hoff
Keyword(s):  
Brain Edema ◽  
Complement Activation ◽  
Autologous Blood ◽  
Complement Cascade ◽  
Edema Formation ◽  
Content Type ◽  
Erythrocyte Lysis ◽  
The Brain ◽  
Brain Edema Formation ◽  
Fine Print

Object. Brain edema formation following intracerebral hemorrhage (ICH) appears to be partly related to erythrocyte lysis and hemoglobin release. Erythrocyte lysis may be mediated by the complement cascade, which then triggers parenchymal injury. In this study the authors examine whether the complement cascade is activated after ICH and whether inhibition of complement attenuates brain edema around the hematoma.Methods. This study was divided into three parts. In the first part, 100 µl of autologous blood was infused into the rats' right basal ganglia, and the animals were killed at 24 and 72 hours after intracerebral infusion. Their brains were tested for complement factors C9, C3d, and clusterin (a naturally occurring complement inhibitor) by using immunohistochemical analysis. In the second part of the study, the rats were killed at 24 or 72 hours after injection of 100 µl of blood. The C9 and clusterin proteins were quantitated using Western blot analysis. In the third part, the rats received either 100 µl of blood or 100 µl of blood plus 10 µg of N-acetylheparin (a complement activation inhibitor). Then they were killed 24 or 72 hours later for measurement of brain water and ion contents. It was demonstrated on Western blot analysis that there had been a sixfold increase in C9 around the hematoma 24 hours after the infusion of 100 µl of autologous blood. Marked perihematomal C9 immunoreactivity was detected at 72 hours. Clusterin also increased after ICH and was expressed in neurons 72 hours later. The addition of N-acetylheparin significantly reduced brain edema formation in the ipsilateral basal ganglia at 24 hours (78.5 ± 0.5% compared with 81.6 ± 0.8% in control animals, p < 0.001) and at 72 hours (80.9 ± 2.2% compared with 83.6 ± 0.9% in control animals, p < 0.05) after ICH.Conclusions. It was found that ICH causes complement activation in the brain. Activation of complement and the formation of membrane attack complex contributes to brain edema formation after ICH. Blocking the complement cascade could be an important step in the therapy for ICH.

Intracerebral infusion of thrombin as a cause of brain edema

1995 ◽  
Vol 83 (6) ◽  
pp. 1045-1050 ◽  
Author(s):  
Kevin R. Lee ◽  
A. Lorris Betz ◽  
Richard F. Keep ◽  
Thomas L. Chenevert ◽  
Seoung Kim ◽  
...  
Keyword(s):  
Brain Edema ◽  
Brain Parenchyma ◽  
Thrombin Inhibitor ◽  
Neurosurgical Procedures ◽  
Edema Formation ◽  
Content Type ◽  
The Right ◽  
The Brain ◽  
Brain Water ◽  
Fine Print

✓ Purified thrombin from an exogenous source is a hemostatic agent commonly used in neurosurgical procedures. The toxicity of thrombin in the brain, however, has not been examined. This study was performed to assess the effect of thrombin on brain parenchyma, using the formation of brain edema as an indicator of injury. Ten µl of test solution was infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later, and the extent of brain edema and ion content were measured. Concentrations of human thrombin as low as 1 U/µl resulted in a significant increase in brain water content. Rats receiving 10 U/µl had a mortality rate of 33% compared to no mortality in the groups receiving smaller doses. Thrombin-induced brain edema was inhibited by a specific and potent thrombin inhibitor, hirudin. A medical grade of bovine thrombin commonly used in surgery also caused brain edema when injected at a concentration of 2 U/µl. Edema formation was prevented by another highly specific thrombin inhibitor, Nα-(2-Naphthalenesulfonylglycyl)-4-dl-phenylalaninepiperidide (α-NAPAP). Thrombininduced brain edema was accompanied by increases in brain sodium and chloride contents and a decrease in brain potassium content. Changes in brain ions were inhibited by both hirudin and α-NAPAP, corresponding to the inhibition of brain water accumulation. This study shows that thrombin causes brain edema when infused into the brain at concentrations as low as 1 U/µl, an amount within the range of concentrations used for topical hemostasis in neurosurgery.

Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats

1998 ◽  
Vol 89 (6) ◽  
pp. 991-996 ◽  
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.

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

1996 ◽  
Vol 85 (1) ◽  
pp. 131-137 ◽  
Author(s):  
Zeev Feldman ◽  
Boris Gurevitch ◽  
Alan A. Artru ◽  
Arieh Oppenheim ◽  
Esther Shohami ◽  
...  
Keyword(s):  
Brain Edema ◽  
Brain Tissue ◽  
Head Trauma ◽  
Neurological Outcome ◽  
Edema Formation ◽  
Content Type ◽  
Standard Curve ◽  
Baseline Values ◽  
Brain Edema Formation ◽  
Fine Print

✓ 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.

Composition of isolated edema fluid in cold-induced brain edema

1979 ◽  
Vol 51 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Jurjen Gazendam ◽  
K. Gwan Go ◽  
Annie K. van Zanten
Keyword(s):  
Cerebrospinal Fluid ◽  
White Matter ◽  
Brain Edema ◽  
Vasogenic Edema ◽  
Colloid Osmotic Pressure ◽  
Freezing Damage ◽  
Content Type ◽  
Edema Fluid ◽  
The Brain ◽  
Fine Print

✓ Edema fluid isolated from cats with cold-induced brain edema was subjected to analysis of electrolyte content, enzyme activities, colloid osmotic pressure and the radioactivity of intravenously injected 99mTc-labeled albumin. The findings corroborate the essential features of vasogenic edema, such as its origin from the blood plasma, its rapid propagation into the white matter of the brain as contrasted with the delayed spread into gray matter, and its contribution to composition of cerebrospinal fluid. Moreover, the elevated activities of cellular enzymes and K+ content of edema fluid point to the admixture with cellular contents due to the freezing damage.

Activation of the complement cascade and increase of clusterin in the brain following a cortical contusion in the adult rat

1996 ◽  
Vol 85 (3) ◽  
pp. 468-475 ◽  
Author(s):  
Bo-Michael Bellander ◽  
Hans von Holst ◽  
Pam Fredman ◽  
Mikael Svensson
Keyword(s):  
Traumatic Injury ◽  
Complement Cascade ◽  
Complement Factor ◽  
Survival Times ◽  
Adult Rats ◽  
Content Type ◽  
Junction Protein ◽  
Cortical Contusion ◽  
The Brain ◽  
Fine Print

✓ The aim of the present study was to examine the glial cell response and the possible involvement of the complement cascade following a cerebral cortical contusion. The lesion was produced using a standardized weight-drop technique in adult rats. The blood-brain barrier was damaged, as demonstrated by a decrease of immunoreactivity for a tight junction protein normally expressed by endothelial cells of small vessels in the central nervous system. Increased immunoreactivity for microglial (OX42) and astroglial cells (glial fibrillary acidic protein), as well as macrophages expressing ED1-immunoreactivity (IR) were found in the vicinity of the lesion at all postoperative survival times (2–14 days). In the present study complement factor C3d- and C9-IR was found around the lesion, indicating that activation of the complement cascade had taken place. Furthermore, immunoreactivity for the putative complement inhibitor clusterin (sulfated glycoprotein-2) was found in some of the injured neurons. The contralateral hemisphere showed no evidence of the reaction found in the ipsilateral hemisphere. The balance between complement activation and complement inhibitors may have an impact on the degenerative components in the brain following traumatic injury and in particular on the events leading to nerve cell death.

Preconditioning with hyperbaric oxygen attenuates brain edema after experimental intracerebral hemorrhage

2007 ◽  
Vol 22 (5) ◽  
pp. 1-6 ◽  
Author(s):  
Zhiyong Qin ◽  
Shuijiang Song ◽  
Guohua Xi ◽  
Robert Silbergleit ◽  
Richard F. Keep ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Hyperbaric Oxygen ◽  
Mapk Pathway ◽  
Autologous Blood ◽  
Neurosurgical Procedures ◽  
Sprague Dawley ◽  
Edema Formation ◽  
Group 2 ◽  
Brain Edema Formation

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.

scholarly journals Release of Bradykinin and Expression of Kinin B2 Receptors in the Brain: Role for Cell Death and Brain Edema Formation After Focal Cerebral Ischemia in Mice

2005 ◽  
Vol 25 (8) ◽  
pp. 978-989 ◽  
Author(s):  
Moritz Gröger ◽  
Diane Lebesgue ◽  
Didier Pruneau ◽  
Jane Relton ◽  
Seong-Woong Kim ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Brain Edema ◽  
Brain Damage ◽  
Receptor Expression ◽  
Experimental Stroke ◽  
Edema Formation ◽  
Receptor Mrna ◽  
The Brain ◽  
Brain Edema Formation

Pharmacological studies using bradykinin B2 receptor antagonists suggest that bradykinin, an early mediator of inflammation and the main metabolite of the kallikrein-kinin system, is involved in secondary brain damage after cerebral ischemia. However, the time-course of bradykinin production and kinin receptor expression as well as the conclusive role of bradykinin B2 receptors for brain damage after experimental stroke have not been elucidated so far. C57/Bl6 mice were subjected to 45 mins of middle cerebral artery occlusion (MCAO) and 2, 4, 8, 24, and 48 h later brains were removed for the analysis of tissue bradykinin concentration and kinin B2 receptor mRNA and protein expression. Brain edema, infarct volume, functional outcome, and long-term survival were assessed in WT and B2−/− mice 24 h or 7 days after MCAO. Tissue bradykinin was maximally increased 12 h after ischemia (three-fold), while kinin B2 receptor mRNA upregulation peaked 24 to 48 h after MCAO (10- to 12-fold versus naïve brain tissue). Immunohistochemistry revealed that kinin B2 receptors were constitutively and widely expressed in mouse brain, were upregulated 2 h after ischemia in cells showing signs of ischemic damage, and remained upregulated in the penumbra up to 24 h after ischemia. B2−/− mice had improved motor function ( P<0.05), smaller infarct volumes (–38%; P<0.01), developed less brain edema (–87%; P<0.05), and survived longer ( P<0.01) as compared with wild-type controls. The current results show that bradykinin is produced in the brain, kinin B2 receptors are upregulated on dying cells, and B2 receptors are involved in cell death and brain edema formation after experimental stroke.

Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by overexpression of interleukin-1 receptor antagonist

2001 ◽  
Vol 95 (4) ◽  
pp. 680-686 ◽  
Author(s):  
Tetsuya Masada ◽  
Ya Hua ◽  
Guohua Xi ◽  
Guo-Yuan Yang ◽  
Julian T. Hoff ◽  
...  
Keyword(s):  
Brain Injury ◽  
Basal Ganglia ◽  
Intracerebral Hemorrhage ◽  
Receptor Antagonist ◽  
Brain Edema ◽  
Inflammatory Reaction ◽  
Interleukin 1 ◽  
Edema Formation ◽  
Content Type ◽  
Fine Print

Object. Adenovirus-mediated overexpression of interleukin-1 receptor antagonist (IL-1ra) attenuates the inflammatory reaction and brain injury that follows focal cerebral ischemia. Recently, an inflammatory reaction after intracerebral hemorrhage (ICH) was identified. In this study the authors examine the hypothesis that overexpression of IL-1ra reduces brain injury (specifically edema formation) after ICH. Methods. Adenoviruses expressing IL-1ra (Ad.RSVIL-1ra) or LacZ, a control protein (Ad.RSVlacZ), or saline were injected into the left lateral cerebral ventricle in rats. On the 5th day after virus injection, 100 µl of autologous blood or 5 U thrombin was infused into the right basal ganglia. Rats with ICH were killed 24 or 72 hours later for measurement of brain water and ion content. Thrombin-treated rats were killed 24 hours later for edema measurements and an assessment of polymorphonuclear leukocyte (PMNL) infiltration by myeloperoxidase (MPO) assay, as well as histological evaluation. Compared with saline-treated and Ad.RSVlacZ—transduced controls, Ad.RSVIL-1ra-transduced rats had significantly attenuated edema in the ipsilateral basal ganglia 3 days after ICH (81.5 ± 0.3% compared with 83.4 ± 0.4% and 83.3 ± 0.5% in control animals). Thrombin-induced brain edema was also reduced in Ad.RSVIL-1ra—treated rats (81.3 ± 0.4% compared with 83.2 ± 0.4% and 82.5 ± 0.4% in control rats). The reduction in thrombin-induced edema was associated with a reduction in PMNL infiltration into the basal ganglia, as assessed by MPO assay (49% reduction) and histological examination. Conclusions. Overexpression of IL-1ra by using an adenovirus vector attenuated brain edema formation and thrombin-induced intracerebral inflammation following ICH. The reduction in ICH-induced edema with IL-1ra may result from reduction of thrombin-induced brain inflammation.

Brain Edema Formation and Complement Activation in a Rat Model of Subarachnoid Hemorrhage

2013 ◽  
pp. 157-161 ◽  
Author(s):  
Chao Zhang ◽  
Jin-Yul Lee ◽  
Richard F. Keep ◽  
Aditya Pandey ◽  
Neeraj Chaudhary ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Edema ◽  
Rat Model ◽  
Complement Activation ◽  
Edema Formation ◽  
Brain Edema Formation
Sign in / Sign up

Export Citation Format

Share Document