A place for ultrastructural analysis of platelets in cerebral ischemic research

Abstract

It is well known that estrogen is neuroprotective through various mechanisms which suggest that sex hormone levels, thrombotic mechanisms, and inflammatory processes are strongly interconnected in predicting the outcome and consequences of cerebral ischemia. Because platelet ultrastructure is altered in conditions like thrombosis and associated with stroke, the question arises whether ultrastructural analyses of platelet morphology may provide further insight into the role of estrogen during ischemic insult. In the current study, a hyperglycemic modification to the two-vessel occlusion model for inducing experimental cerebral ischemia was employed, in order to correlate neural tissue integrity levels between three experimental groups to corresponding platelet ultrastructure so as to determine whether there is an association between cerebral ischemia and the presence of inflammatory or necrotic platelet ultrastructure. It is apparent in the results that under the influence of estrogen in cyclic or intact females, there is lesser neural tissue damage as well as a reduced degree of inflammation evident in platelet activation morphology when compared to males and acyclic or ovariectomized females. It is unmistakable that neural injury is closely shadowed, if not preceded, by inflammatory changes in the coagulation system, particularly manifested in platelet ultrastructure. It is therefore suggested that platelets may indeed be used successfully to follow the progression of events of cerebral ischemia and possibly assist in the assessment of treatment strategies and their effects on hemostasis.

Interleukin‐12 and its procoagulant effect on erythrocytes, platelets and fibrin(ogen): the lesser known side of inflammation

“…One of the hallmarks of inflammation is a pathological coagulation system, and this is the direct result of upregulated circulating inflammatory molecules. During inflammation, platelets become aggregated and activated, with microparticle formation; RBCs become eryptotic and also produce microparticles (Van Der Spuy & Pretorius, ; Gasparyan et al , ; Pretorius & Kell, ; Bester & Pretorius, ; Pretorius et al , ,c; Soma et al , ); and pathological plasma clots form, mainly due to pathological changes in the healthy fibrin(ogen) protein structure (Kell & Pretorius, ; Pretorius et al , ). Therefore, by studying the effect of individual inflammatory molecules on RBCs, platelets and fibrin(ogen) we may improve our understanding of the inflammatory response and provide important advances in understanding both inflammation regulation and the resulting pathophysiological coagulation.…”

Pathological Clotting and Deep Vein Thrombosis in Patients with HIV

“…27 Platelets aggregate with leukocytes in areas of ischemia/reperfusion injury. 29 The activated platelets interact with and signal to other inflammatory cells, such as leukocytes, and release their granules in high concentrations. Between 0.26 and 7.6% of HIV-infected patients will have venous thromboembolism (VTE) and activated platelets have been suggested as the etiology.…”

Hyperglycemic Modification to Classical Two-Vessel Occlusion for Inducing Transient Cerebral Ischemia in Sprague-Dawley Rats

“…In their groups, it was found that male (NTI = 23.897%) rats displayed significantly more neural tissue injury than acyclic females (NTI = 13.466%) who also in turn displayed significantly more neural tissue injury than cyclic females (NTI = 9.217%) (Figure 4). Previously, neural tissue injury of this subset of animals was correlated to alterations in platelet ultrastructure at specific time points to establish that neural injury and the fluctuation of inflammation associated with such injury is mirrored by changes in platelet morphology [15].…”

“…From the neural tissue injury results, it can be deduced that subsequent to cerebral ischemia cyclic female neural tissue presents the lowest overall loss of integrity with high estradiol levels curbing inflammation early on [15] and initiating recovery by stalling apoptosis [22,23]. The neural tissue of males is shown to deteriorate significantly in the absence of adequate estradiol due to an inability to curb the inflammatory response and suppress apoptosis.…”

“…Acyclic females, also with low estradiol levels, display a smaller degree of injury to males in this study. Though the lack of estrogen in acyclic females definitely lessens neuroprotection, there appears to be some inherent degree of protection, at least two weeks subsequent to bilateral ovariectomy, from the insult of mild cerebral ischemic injury when compared to males; possibly due to an inherent state of inflammation termed thrombotic preparedness [15,24,25] which may lessen the initial inflammatory shock of ischemic injury to the neural tissue.…”