Focal Ischaemic Infarcts Expand Faster in Cerebellar Cortex than Cerebral Cortex in a Mouse Photothrombotic Stroke Model

Abstract

It is generally accepted that the cerebellum is particularly vulnerable to ischaemic injury, and this may contribute to the high mortality arising from posterior circulation strokes. However, this has not been systematically examined in an animal model. This study compared the development and resolution of matched photothrombotic microvascular infarcts in the cerebellar and cerebral cortices in adult 129/SvEv mice of both sexes. The photothrombotic lesions were made using tail vein injection of Rose Bengal with a 532 nm laser projected onto a 2 mm diameter aperture over the target region of the brain (with skull thinning). Infarct size was then imaged histologically following 2 h to 30-day survival using serial reconstruction of haematoxylin and eosin stained cryosections. This was complemented with immunohistochemistry for neuron and glial markers. At 2 h post-injury, the cerebellar infarct volume averaged ~ 2.7 times that of the cerebral cortex infarcts. Infarct volume reached maximum in the cerebellum in a quarter of the time (24 h) taken in the cerebral cortex (4 days). Remodelling resolved the infarcts within a month, leaving significantly larger residual injury volume in the cerebellum. The death of neurons in the core lesion at 2 h was confirmed by NeuN and Calbindin immunofluorescence, alongside activation of astrocytes and microglia. The latter persisted in the region within and surrounding the residual infarct at 30 days. This comparison of acute focal ischaemic injuries in cerebellar and cerebral cortices provides direct confirmation of exacerbation of neuropathology and faster kinetics in the cerebellum.

Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury

“…This revealed a high capacity of microglia to activate after a disruption in tissue homeostasis. Recently, a series of studies revealed the presence of activated microglia in the acute phase [ 22 ], sub-acute phase [ 23 ], and chronic phase [ 24 ] of IS. The aforementioned morphology changes are associated with different activated microglia functions.…”

Hemispheric cortical atrophy and chronic microglial activation following mild focal ischemic stroke in adult male rats

“…Inflammation is a universal response to stroke that has been well described clinically and in animal models as a target for therapeutic intervention (Jayaraj et al, 2019;Shi et al, 2019). The vast majority of these studies have limited their analyses to the acute and subacute period after injury, that is days or weeks after large strokes (Gorlamandala et al, 2018;Morioka et al, 1993;Price et al, 2006).…”

Investigating The Efficiency of Photothrombosis-Associated Focal Cerebral Ischemia By Monitoring Histopathological Changes and Neurobehavioral Performance in Model of Mouse

“…Along with conventional approaches to induce ischemic stroke, thromboembolic ischemia is an alternative modality used via the injection of thrombin directly into the middle cerebral artery [6]. In recent decades, the acute photothrombotic (PT) stroke model has been developed for the focal ischemic changes by local infusion photo-sensitive dye into the venous circulation [7,8]. Initially, Rosenblum and El-Sabban in 1977 introduced the PT model which later improved by Watson in 1985 [9].…”