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  • Author or Editor: Melanie D. King x
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Melanie D. King, D. Jay McCracken, F. Marlene Wade, Steffen E. Meiler, Cargill H. Alleyne Jr. and Krishnan M. Dhandapani

Object

Intracerebral hemorrhage (ICH) is associated with significant morbidity and mortality. Acute hematoma enlargement is an important predictor of neurological injury and poor clinical prognosis; but neurosurgical clot evacuation may not be feasible in all patients and treatment options remain largely supportive. Thus, novel therapeutic approaches to promote hematoma resolution are needed. In the present study, the authors investigated whether the curry spice curcumin limited neurovascular injury following ICH in mice.

Methods

Intracerebral hemorrhage was induced in adult male CD-1 mice by intracerebral administration of collagenase or autologous blood. Clinically relevant doses of curcumin (75–300 mg/kg) were administered up to 6 hours after ICH, and hematoma volume, inflammatory gene expression, blood-brain barrier permeability, and brain edema were assessed over the first 72 hours. Neurological assessments were performed to correlate neurovascular protection with functional outcomes.

Results

Curcumin increased hematoma resolution at 72 hours post-ICH. This effect was associated with a significant reduction in the expression of the proinflammatory mediators, tumor necrosis factor–α, interleukin-6, and interleukin-1β. Curcumin also reduced disruption of the blood-brain barrier and attenuated the formation of vasogenic edema following ICH. Consistent with the reduction in neuroinflammation and neurovascular injury, curcumin significantly improved neurological outcome scores after ICH.

Conclusions

Curcumin promoted hematoma resolution and limited neurological injury following ICH. These data may indicate clinical utility for curcumin as an adjunct therapy to reduce brain injury and improve patient outcome.

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Melanie D. King, Melissa D. Laird, Sangeetha Sukumari Ramesh, Patrick Youssef, Basheer Shakir, John R. Vender, Cargill H. Alleyne Jr. and Krishnan M. Dhandapani

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.