Repair-related molecular changes during recovery phase of ischemic stroke in female rats

Maryam Mostajeran; Lars Edvinsson; Hilda Ahnstedt; Kajsa Arkelius; Saema Ansar

doi:10.1186/s12868-022-00696-x

Repair-related molecular changes during recovery phase of ischemic stroke in female rats

BMC Neurosci. 2022 Apr 12;23(1):23. doi: 10.1186/s12868-022-00696-x.

Authors

Maryam Mostajeran¹, Lars Edvinsson¹, Hilda Ahnstedt², Kajsa Arkelius³, Saema Ansar⁴

Affiliations

¹ Division of Experimental Vascular Research, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
² Department of Neurology, McGovern Medical School at University of Texas Health Science Center at Houston, Houston, TX, USA.
³ Applied Neurovascular Research, Neurosurgery, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
⁴ Applied Neurovascular Research, Neurosurgery, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden. Saema.Ansar@med.lu.se.

Abstract

Background: Some degree of spontaneous recovery is usually observed after stroke. Experimental studies have provided information about molecular mechanisms underlying this recovery. However, the majority of pre-clinical stroke studies are performed in male rodents, and females are not well studied. This is a clear discrepancy when considering the clinical situation. Thus, it is important to include females in the evaluation of recovery mechanisms for future therapeutic strategies. This study aimed to evaluate spontaneous recovery and molecular mechanisms involved in the recovery phase two weeks after stroke in female rats.

Methods: Transient middle cerebral artery occlusion was induced in female Wistar rats using a filament model. Neurological functions were assessed up to day 14 after stroke. Protein expression of interleukin 10 (IL-10), transforming growth factor (TGF)-β, neuronal specific nuclei protein (NeuN), nestin, tyrosine-protein kinase receptor Tie-2, extracellular signal-regulated kinase (ERK) 1/2, and Akt were evaluated in the peri-infarct and ischemic core compared to contralateral side of the brain at day 14 by western blot. Expression of TGF-β in middle cerebral arteries was evaluated by immunohistochemistry.

Results: Spontaneous recovery after stroke was observed from day 2 to day 14 and was accompanied by a significantly higher expression of nestin, p-Akt, p-ERK1/2 and TGF-β in ischemic regions compared to contralateral side at day 14. In addition, a significantly higher expression of TGF-β was observed in occluded versus non-occluded middle cerebral arteries. The expression of Tie-2 and IL-10 did not differ between the ischemic and contralateral sides.

Conclusion: Spontaneous recovery after ischemic stroke in female rats was coincided by a difference observed in the expression of molecular markers. The alteration of these markers might be of importance to address future therapeutic strategies.

Keywords: Female; Ischemic stroke; Molecular changes; Repair mechanisms; Spontaneous recovery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Ischemia*
Female
Infarction, Middle Cerebral Artery / drug therapy
Interleukin-10
Ischemic Stroke*
Male
Nestin
Pregnancy
Proto-Oncogene Proteins c-akt
Rats
Rats, Wistar
Recovery of Function / physiology
Stroke* / metabolism
Transforming Growth Factor beta

Substances

Nestin
Transforming Growth Factor beta
Interleukin-10
Proto-Oncogene Proteins c-akt