Special Issue of Translational Stroke: Importance of Sex in the Pathophysiology and Treatment of Acute CNS Repair

Abstract

Over the last several decades, basic research studies as well as clinical programs have emphasized the importance of gender on injury mechanisms leading to the devastating consequences of CNS injury. Also, the importance of gender in targeting these complicated pathomechanisms with various therapeutic interventions has also been emphasized. Indeed, several early investigations reported differences in CNS vulnerability between male and female animals having similar types of insults including cerebral ischemia and neurotrauma. Other studies reported the importance of circulating hormones on affecting the response of the brain to damage, thus emphasizing various endogenous protective mechanisms that may be present in some genders. The present issue includes nine papers that report different aspects of gender-specific differences in the CNS response to damage and how this information can help identify novel therapeutic treatments for these devastating disorders. Each article is written by experts in the field and is well organized, clear, and informative. We feel that this special issue is timely and will be of value to many scientists and clinicians working in the field of CNS injury and repair.This special issue includes several chapters related to gender-specific differences in response to cerebral ischemia and stroke. Alkayed and colleagues provide a timely review regarding the role of soluble epoxide hydrolase, an enzyme responsible for the degradation of vasoprotective eicosatrienoic acids, and its contributions to the sexual dimorphic nature of stroke [1]. Because endothelial dysfunction and alterations in cerebral blood flow play a major role in stroke outcome, sex differences between processes downstream from estrogen including soluble epoxide hydrogenase appear to be a particularly important factor. In another article, Koellhoffer and McCullough discuss estrogen and inflammation and its interaction with aging [2]. Available clinical literature emphasizes that the risk of stroke in elderly women exceeds that of men, and it is clear that in some situations, estrogen can have proinflammatory effects. This observation is in contrast to the fact that women have a lower incidence of stroke throughout most of their life span which is possibly due to the beneficial effects of steroids including estrogen. This chapter therefore addresses the important concept of what therapeutic options can be utilized to improve recovery once the stroke has occurred.Furthermore, Raval and colleagues focus on mechanisms by which oral contraceptives and smoking-derived nicotine may inhibit estrogen signaling that could be responsible for the severe ischemic damage seen in females where increased risk and severity of cerebral ischemia are appreciated [3]. This chapter summarizes recent laboratory studies including the report that the severity of ischemic damage in the hippocampus is far greater in females simultaneously exposed to oral contraceptives and cigarette smoking compared to nicotine alone. The authors hypothesize that these...

Neurovascular Events After Subarachnoid Hemorrhage: Focusing on Subcellular Organelles

“…Moreover, considering the significance of EBI on the outcome of SAH, more efforts on EBI are required to develop a novel treatment paradigm [14, 51]. Finally, sex differences in the organelles need to be emphasized in experimental studies [4, 19]. …”

Mammalian Sterile20-like Kinases: Signalings and Roles in Central Nervous System

“…These alterations in CNS would normally result in sensory, motor and cognitive dysfunction or even death. Spontaneous regeneration of neurons is not possible, leaving few treatment options for patients with CNS injuries or diseases [ 15 , 16 ].…”