Cerebellar Blood Flow and Gene Expression in Crossed Cerebellar Diaschisis after Transient Middle Cerebral Artery Occlusion in Rats

Abstract

Crossed cerebellar diaschisis (CCD) is a state of hypoperfusion and hypometabolism in the contralesional cerebellar hemisphere caused by a supratentorial lesion, but its pathophysiology is not fully understood. We evaluated chronological changes in cerebellar blood flow (CbBF) and gene expressions in the cerebellum using a rat model of transient middle cerebral artery occlusion (MCAO). CbBF was analyzed at two and seven days after MCAO using single photon emission computed tomography (SPECT). DNA microarray analysis and western blotting of the cerebellar cortex were performed and apoptotic cells in the cerebellar cortex were stained. CbBF in the contralesional hemisphere was significantly decreased and this lateral imbalance recovered over one week. Gene set enrichment analysis revealed that a gene set for “oxidative phosphorylation” was significantly upregulated while fourteen other gene sets including “apoptosis”, “hypoxia” and “reactive oxygen species” showed a tendency toward upregulation in the contralesional cerebellum. MCAO upregulated the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the contralesional cerebellar cortex. The number of apoptotic cells increased in the molecular layer of the contralesional cerebellum. Focal cerebral ischemia in our rat MCAO model caused CCD along with enhanced expression of genes related to oxidative stress and apoptosis.

Secondary Cerebellar Cortex Injury in Albino Male Rats after MCAO: A Histological and Biochemical Study

“…The results of H&E stained cerebellar sections exhibited degenerative histological changes in the MCAO group. Similar findings were observed by [ 7 , 23 ]. Jie and his colleagues found apoptosis of neural cells of the cerebellar cortex in the MCAO group by the electron transmission microscope and further confirmed the results by TUNEL assay.…”

“…In 1981, in the presence of a hemispheric stroke, Baron et al described crossed cerebral diaschisis (CCD) [ 6 ], a supratentorial lesion that causes hypoperfusion and hypometabolism in the contralesionally cerebellar hemisphere. However, the etiology of CCD is unknown [ 7 ]. To date, CCD mechanisms have been thought to start by interrupting the exiting input of the cerebellum, primarily through a cortico-pontocerebellar pathway [ 8 , 9 ].…”

Transplantation of modified human bone marrow‐derived stromal cells affords therapeutic effects on cerebral ischemia in rats

“…MCAO was induced according to the intraluminal suture method used in our previous studies. 25 , 27 , 28 , 29 Under general anesthesia (2% sevoflurane in 70% N₂O and 30% O₂), a 4–0 monofilament nylon suture with silicone‐coated tip (Xantopren L blue & ACTIVATOR Universal Liquid, Heraeus Kulzer GmbH & Co. KG) was inserted through an arteriotomy of the right external carotid artery into the origin of the right MCA. After MCAO for 90 min, the filament was withdrawn to restore the blood flow and the wound was sutured.…”

Key Phytochemicals and Biological Functions of Chuanxiong Rhizoma Against Ischemic Stroke: A Network Pharmacology and Experimental Assessment

“…The seed node of this cluster was CREB binding protein (CREBBP) (Figure 4E). CREBBP (Gouveia et al, 2017), NFE2L2 (Kidani et al, 2020) and PARP1 (Liu et al, 2021) are known for their roles in the pathogenesis of stroke and post-stroke neurovascular remodeling and FIGURE 2 | Enrichment analysis of the CR potential targets. GO functional (A) and KEGG pathway enrichment analysis (B) of 376 targets of CR main phytochemicals were identified using the ClusterProfiler package, in which the significance threshold is set as p value < 0.05.…”