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Updated: Apr 29, 2026
A Rat Model of Middle Cerebral Artery Occlusion/Reperfusion Without Damaging the Anatomical Structure of Cerebral Vessels
Published on: May 17, 2024
The effects of fludarabine on rat cerebral ischemia
Qian Xu1, Chunjuan Jiang, Yutao Rong
1Department of Radiology, Affiliated Hospital of Xuzhou Medical College, No. 99 West Huai-hai Road, Xuzhou, Jiangsu Province, 221002, People's Republic of China, xuqianxz@126.com.
Abstract:
Cerebral ischemic injury involves a variety of cellular and molecular events. Signal transducers and activators of transcription-1 (STAT-1) activation is associated with neuronal cell death and contributes to ischemic injury. The effects of fludarabine, a specific inhibitor of STAT1 protein, on cerebral ischemic/reperfusion (I/R) injury were studied in a rat model. Rats subjected to I/R injury were either treated with intra-cerebroventricular injection of fludarabine (5,000 μM, 10 μl) or saline 20 min before middle cerebral artery occlusion (MCAO). MR examinations including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and perfusion-weighted imaging (PWI) were performed after I/R period. Then rat brains were sectioned for triphenyltetrazolium chloride (TTC) stains, analyzed by Western blot and TUNEL staining of apoptosis. It was found that fludarabine treatment decreased the infarct volume of the cerebrum and the number of apoptotic neural cells in the ischemic brain. Compared to saline-treated group, the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) in the ischemic region were greater, and the mean transit time (MTT) was shortened in the fludarabine-treated group. Moreover, fludarabine inhibited the expression level of phosphorylated STAT1 (P-STAT1) in neural cells after I/R injury, whereas the expression of phosphorylated STAT3 (P-STAT3) was increased. Therefore, we concluded that fludarabine administrated in early stage of cerebral ischemia had neuroprotective effects, and the underlying mechanism could be mediated through inhibiting STAT1 phosphorylation and activating the cross regulation between STAT1 and STAT3 in neural cells.
Insights
Fludarabine treatment reduced brain damage and neuronal death in rats following cerebral ischemia. This neuroprotective effect is linked to inhibiting signal transducer and activator of transcription-1 (STAT-1) phosphorylation.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Cerebral ischemic injury involves complex cellular and molecular processes.
- Signal transducers and activators of transcription-1 (STAT-1) activation is implicated in neuronal cell death and ischemic brain injury.
Purpose of the Study:
- To investigate the neuroprotective effects of fludarabine, a STAT1 inhibitor, on cerebral ischemic/reperfusion (I/R) injury in a rat model.
- To elucidate the underlying molecular mechanisms involving STAT1 and STAT3 signaling pathways.
Main Methods:
- Rats underwent middle cerebral artery occlusion (MCAO) to induce I/R injury and were treated with fludarabine or saline.
- Magnetic resonance (MR) imaging (T2WI, DWI, PWI) was performed to assess injury.
- Brain sections were analyzed using triphenyltetrazolium chloride (TTC) staining, Western blot for protein expression, and TUNEL staining for apoptosis.
Main Results:
- Fludarabine treatment significantly decreased cerebral infarct volume and the number of apoptotic neural cells.
- MR imaging showed increased apparent diffusion coefficient (ADC) and cerebral blood volume (CBV), and shortened mean transit time (MTT) in fludarabine-treated rats.
- Fludarabine inhibited phosphorylated STAT1 (P-STAT1) expression while increasing phosphorylated STAT3 (P-STAT3) expression.
Conclusions:
- Early-stage administration of fludarabine exerts neuroprotective effects against cerebral ischemia.
- The mechanism involves inhibiting STAT1 phosphorylation and modulating the cross-regulation between STAT1 and STAT3 signaling pathways in neural cells.
