Learn More
The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after(More)
OBJECTIVE Topiramate, valproate, propranolol, amitriptyline, and methysergide have been widely prescribed for migraine prophylaxis, but their mechanism or site of action is uncertain. Cortical spreading depression (CSD) has been implicated in migraine and as a headache trigger and can be evoked in experimental animals by electrical or chemical stimulation.(More)
The initial phase in the development of a migraine is still poorly understood. Here, we describe a previously unknown signaling pathway between stressed neurons and trigeminal afferents during cortical spreading depression (CSD), the putative cause of migraine aura and headache. CSD caused neuronal Pannexin1 (Panx1) megachannel opening and caspase-1(More)
Stroke, a brain attack, is the third leading cause of death in the Western world. Worldwide, about 5.5 million people died from stroke in 1999 — approximately 10% of all deaths. There are more than 3.5 million survivors in the United States alone, and the disease remains a major cause of disability. In practice,'stroke' refers to an umbrella of conditions(More)
Pericytes are located at periphery of the microvessel wall and wrap it with their processes. They communicate with other cells of the neurovascular unit by direct contact or through signaling pathways and regulate several important microcirculatory functions. These include development and maintenance of the blood-brain barrier (BBB), distribution of the(More)
Here we show that ischemia induces sustained contraction of pericytes on microvessels in the intact mouse brain. Pericytes remain contracted despite successful reopening of the middle cerebral artery after 2 h of ischemia. Pericyte contraction causes capillary constriction and obstructs erythrocyte flow. Suppression of oxidative-nitrative stress relieves(More)
Cell death after traumatic brain injury (TBI) evolves over days to weeks. Despite advances in understanding biochemical mechanisms that contribute to posttraumatic brain cell death, the time course of cell injury, death, and removal remains incompletely characterized in experimental TBI models. In a mouse controlled cortical impact (CCI) model, plasmalemma(More)
NeuN immunoreactivity is used as a specific marker for neurons. The number of NeuN-positive cells decreases under pathological conditions. This finding is usually considered as an evidence of neuronal loss. However, decrease in NeuN labeling may also be caused by depletion of the protein or loss of its antigenicity. Hence, we have investigated the(More)
BACKGROUND AND PURPOSE Both necrotic and apoptotic cell death mechanisms are activated after cerebral ischemia. However, whether they are concomitantly active in the same cell or in discrete cell populations is not known. METHODS We investigated activation of both pathways at the cellular level in mice brains subjected to transient or permanent focal(More)
Caspases play an important role as mediators of cell death in acute and chronic neurological disorders. Although peptide inhibitors of caspases provide neuroprotection, they have to be administered intracerebroventricularly because they cannot cross the blood-brain barrier (BBB). Herein, we present a nanocarrier system that can transfer chitosan nanospheres(More)