Protective effects of astaxanthin on subarachnoid hemorrhage-induced early brain injury: Reduction of cerebral vasospasm and improvement of neuron survival and mitochondrial function

OBJECTIVEDelayed brain injury (DBI) is considered one of the most important causes of mortality and morbidity after subarachnoid hemorrhage (SAH). However, no suitable experimental rat endovascular perforation (EVP) SAH model was available for investigating DBI. The authors added early cerebral hypoperfusion to a mild EVP SAH model by unilateral common carotid artery occlusion (UCCAO) 24 hours after induction of SAH to mimic the clinical course of early cerebral hypoperfusion after SAH.METHODSA total of 109 adult male Sprague-Dawley rats were randomly divided into 2 groups: no SAH and SAH. Next, no-SAH rats were randomly divided on day 1 into 2 groups: sham and UCCAO. SAH rats with a neurological score of 15 or greater were randomly divided into 2 groups: SAH − UCCAO and SAH + UCCAO group.RESULTSThe mild SAH model had a lower mortality rate of 5.4% within the first 24 hours. No rat died in the SAH + UCCAO group until day 7. DBI as well as early brain injury (EBI), reactive astrogliosis, and cerebral vasospasm significantly worsened in the SAH + UCCAO group.CONCLUSIONSThe present SAH + UCCAO model can simulate EBI with aggravation of reactive astrogliosis, cerebral vasospasm, and DBI but without high mortality.

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Abstract WP256: Pretreatment of Rosuvastatin Ameliorates Early Brain Injury after Subarachnoid Hemorrhage through the Inhibition of Microglial Activation in Rats.

Stroke ◽

10.1161/str.44.suppl_1.awp256 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Ken Uekawa ◽

Yu Hasekawa ◽

Mingjie Ma ◽

Takashi Nakagawa ◽

Tetsuji Katayama ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Brain Edema ◽

Microglial Activation ◽

Inflammatory Responses ◽

Early Brain Injury ◽

Water Soluble ◽

Vehicle Group ◽

Protective Effects ◽

Anti Inflammatory

BACKGROUND AND PURPOSE: We investigated the protective effects of pretreatment of oral-administered rosuvastatin, a water soluble HMG-CoA reductase inhibitor, on early brain injury (EBI) after subarachnoid hemorrhage (SAH). METHOD: Male Sprague-Dawley rats were operated on with endovascular perforation model and randomly divided into 4 groups: sham-operated, SAH+vehicle, SAH+1mg/kg, or 10mg/kg rosuvastatin. The animals in treatment groups were administered with daily oral rosuvastatin from 7 days before to 1 day after operation. All rats were evaluated regarding neurofunction, brain edema, and blood-brain barrier (BBB) disruption at 24 hours after SAH. Anti-inflammatory responses were also conducted using Western blot and immunohistochemistry at 24 hours after SAH. RESULTS: Compared with the vehicle group, rosuvastatin significantly improved the neurofunction score (modified Garcia score/ 22: 13.0±1.6 vs 17.0±1.0, P <0.05) , brain edema (brain water content: 79.11±0.15% vs 78.68±0.09%, P <0.05) , and BBB disruption (IgG extravasation); data are showed as a mean±SEM. Rosuvastatin reduced number of activated microglial cells , activation of nuclear factor-kappa B(NF-kB), and expression of tumor necrosis factor-alpha (TNF-α) , which were considered as markers of inflammatory response from microglia, and downregulated the expression of neuronal cyclooxygenase-2 (COX-2) and endothelial matrix metalloproteinase-9 (MMP-9). CONCLUSION: The current study showed that pretreatment of rosuvastatin induced anti-inflammatory processes through inhibition of microglial activation and thereby attenuated early brain injury. Rosuvastatin seems to be a promising agent for treatment of SAH.

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Protective effects of recombinant osteopontin on early brain injury after subarachnoid hemorrhage in rats*

Critical Care Medicine ◽

10.1097/ccm.0b013e3181c027ae ◽

2010 ◽

Vol 38 (2) ◽

pp. 612-618 ◽

Cited By ~ 73

Author(s):

Hidenori Suzuki ◽

Robert Ayer ◽

Takashi Sugawara ◽

Wanqiu Chen ◽

Takumi Sozen ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Early Brain Injury ◽

Protective Effects

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Elucidating novel mechanisms of brain injury following subarachnoid hemorrhage: an emerging role for neuroproteomics

Neurosurgical FOCUS ◽

10.3171/2009.10.focus09223 ◽

2010 ◽

Vol 28 (1) ◽

pp. E10 ◽

Cited By ~ 33

Author(s):

Melanie D. King ◽

Melissa D. Laird ◽

Sangeetha Sukumari Ramesh ◽

Patrick Youssef ◽

Basheer Shakir ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Cerebral Vasospasm ◽

Neurological Outcome ◽

Scientific Discovery ◽

Delayed Cerebral Ischemia ◽

Early Brain Injury ◽

Neurological Injury ◽

Brain Physiology ◽

Potential Biomarker

Subarachnoid hemorrhage (SAH) is a devastating neurological injury associated with significant patient morbidity and death. Since the first demonstration of cerebral vasospasm nearly 60 years ago, the preponderance of research has focused on strategies to limit arterial narrowing and delayed cerebral ischemia following SAH. However, recent clinical and preclinical data indicate a functional dissociation between cerebral vasospasm and neurological outcome, signaling the need for a paradigm shift in the study of brain injury following SAH. Early brain injury may contribute to poor outcome and early death following SAH. However, elucidation of the complex cellular mechanisms underlying early brain injury remains a major challenge. The advent of modern neuroproteomics has rapidly advanced scientific discovery by allowing proteome-wide screening in an objective, nonbiased manner, providing novel mechanisms of brain physiology and injury. In the context of neurosurgery, proteomic analysis of patient-derived CSF will permit the identification of biomarkers and/or novel drug targets that may not be intuitively linked with any particular disease. In the present report, the authors discuss the utility of neuroproteomics with a focus on the roles for this technology in understanding SAH. The authors also provide data from our laboratory that identifies high-mobility group box protein-1 as a potential biomarker of neurological outcome following SAH in humans.

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