Pathological Comparisons of the Hippocampal Changes in the Transient and Permanent Middle Cerebral Artery Occlusion Rat Models

Abstract

Ischemic strokes are categorized by permanent or transient obstruction of blood flow, which impedes delivery of oxygen and essential nutrients to brain. In the last decade, the therapeutic window for tPA has increased from 3 to 5–6 h, and a new technique, involving the mechanical removal of the clot (endovascular thrombectomy) to allow reperfusion of the injured area, is being used more often. This last therapeutic approach can be done until 24 h after stroke onset. Due to this fact, more acute ischemic stroke patients are now being recanalized, and so tMCAO is probably the “best” model to address these patients that have a potential good outcome in terms of survival and functional recovery. However, permanent occlusion patients are also important, not only to increase survival rate but also to improve functional outcomes, although these are more difficult to achieve. So, both models are important, and which target different stroke patients in the clinical scenario. Hippocampus has a vital role in memory and cognition, is prone to ischemic induced neurodegeneration. This study was designed to delineate the molecular, pathological, and neurological changes in rat models of t-MCAO, permanent MCAO (pMCAO), and pMCAO with diabetic conditions in hippocampal tissue. Our results showed that these three models showed distinct discrepancies at numerous pathological process, including key signaling molecules involved in neuronal apoptosis, glutamate induced excitotoxicity, neuroinflammation, oxidative stress, and neurotrophic changes. Our result suggests that the two commonly used MCAO models exhibited tremendous differences in terms of neuronal cell loss, glutamate excitotoxic related signaling, synaptic transmission markers, neuron inflammatory and oxidative stress molecules. These differences may reflect the variations in different models, which may provide valuable information for mechanistic and therapeutic inconsistences as experienced in both preclinical models and clinical trials.

A New Rat Model of Chronic Cerebral Hypoperfusion Resulting in Early-Stage Vascular Cognitive Impairment

“…In the BCAO group, the cerebral blood flow presents a sharp decline leading to acute ischemic impairment in cerebral microcirculation, acute cerebral ischemic infarction, and high mortality rates (Naritomi, 1991) regardless of compensation via vertebral arteries and collateral circulation that typically contributes to CBF recovery (Kato et al, 2019). Thus, we deduce that BCAO rats are more akin to models of acute focal cerebral ischemia caused by middle cerebral artery occlusion (Naritomi, 1991;Shah et al, 2019). This may explain the differences in FA value changes between the BCAS and BCAO models.…”

Carveol a Naturally-Derived Potent and Emerging Nrf2 Activator Protects Against Acetaminophen-Induced Hepatotoxicity

“…Moreover, role of the JNK pathway in inflammatory cascades and cellular death has been strongly established ( Ali A et al, 2020 ), and ROS and inflammatory cytokines can trigger JNK activation ( Ali A et al, 2020 ; Ali T et al, 2020 ; Ling et al, 2020 ). Furthermore, the p-JNK pathway has been implicated in various animal models and human diseases ( Shah et al, 2018 ; Li and Liu, 2019 ; Ali A et al, 2020 ; Ling et al, 2020 ; Malik et al, 2020 ), and the downregulation or inhibition of this pathway has been found to contribute to the protective strategy ( Shah et al, 2019 ). We observed similar activities in the APAP-intoxicated group, and carveol significantly reduced p-JNK expression.…”

Potent Natural Antioxidant Carveol Attenuates MCAO-Stress Induced Oxidative, Neurodegeneration by Regulating the Nrf-2 Pathway

“…Immunohistochemical staining was performed as previously described with minor modifications (Shah et al, 2019c;Iqbal et al, 2020). The slides were processed for the antigen retrieval step (enzymatic method), then washed with PBS.…”