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Updated: Aug 16, 2026
Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion
Published on: March 1, 2019
Molecular changes in nNOS protein expression within the ventrolateral medulla following transient focal ischemia
Ahmmed Ally1, Surya M Nauli, Timothy J Maher
1Department of Pharmaceutical Sciences, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, 901 South Flagler Drive, West Palm Beach, FL 33416, USA. ahmmed_ally@pba.edu
Abstract:
The majority of human strokes involve an occlusion of the middle cerebral artery and subsequent damage to the brain tissues it perfuses. We have previously reported that reflex cardiovascular changes during a static muscle contraction are attenuated following transient middle cerebral artery occlusion (MCAO) and reperfusion [A. Ally, S.M. Nauli, T.J. Maher, Cardiovascular responses and neurotransmission in the ventrolateral medulla during skeletal muscle contraction following transient middle cerebral artery occlusion and reperfusion, Brain Res. 952 (2002) 176-187]. We hypothesized that the attenuation is a result of altered expression of neuronal nitric oxide synthase (nNOS) within the rostral (RVLM) and caudal ventrolateral medulla (CVLM). In this study, we have compared cardiovascular responses and nNOS protein expression within the four quadrants, i.e., left and right sides of both RVLM and CVLM in sham-operated rats (n = 10) and in rats with a temporary 90-min left-sided MCAO followed by 24 h reperfusion (n = 10). Increases in mean arterial pressure during a static muscle contraction were significantly attenuated in MCAO rats when compared to sham rats. The transient ischemia reduced nNOS expression within the ipsilateral RVLM quadrant compared to the contralateral RVLM or RVLM quadrants of control rats. In contrast, compared to sham rats and the right CVLM quadrant of MCAO rats, nNOS expression was significantly augmented in the ipsilateral CVLM in left-sided MCAO rats. These data suggest that the attenuation of cardiovascular responses during static muscle contraction in MCAO rats is partly due to a reduction in nNOS expression within the ipsilateral RVLM and an overexpression of nNOS abundance within the ipsilateral CVLM. Results demonstrate that nNOS expression within the medulla plays a significant role in mediating cardiovascular responses during static exercise in intact and pathophysiological conditions.
Insights
Following middle cerebral artery occlusion (MCAO), cardiovascular responses during exercise are blunted due to altered neuronal nitric oxide synthase (nNOS) expression in the ventrolateral medulla. This study investigates nNOS changes in specific brain regions post-MCAO.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Stroke Research
Background:
- Middle cerebral artery occlusion (MCAO) is a common cause of stroke, leading to brain tissue damage.
- Previous research indicated attenuated reflex cardiovascular changes during static muscle contraction after transient MCAO.
- The precise mechanisms behind this attenuation, particularly involving the ventrolateral medulla, require further elucidation.
Purpose of the Study:
- To investigate the hypothesis that altered neuronal nitric oxide synthase (nNOS) expression in the rostral (RVLM) and caudal ventrolateral medulla (CVLM) underlies the attenuated cardiovascular responses post-MCAO.
- To compare nNOS protein expression in different quadrants of the RVLM and CVLM between sham-operated and MCAO rats.
Main Methods:
- Comparison of cardiovascular responses during static muscle contraction in sham-operated rats (n=10) and rats with transient left-sided MCAO (n=10) followed by 24h reperfusion.
- Assessment of nNOS protein expression within the ipsilateral and contralateral RVLM and CVLM quadrants using Western blotting.
- Statistical analysis to determine significant differences in cardiovascular parameters and nNOS expression between groups.
Main Results:
- Mean arterial pressure increases during static muscle contraction were significantly attenuated in MCAO rats compared to sham rats.
- MCAO led to reduced nNOS expression in the ipsilateral RVLM but significantly increased nNOS expression in the ipsilateral CVLM.
- These changes in nNOS expression differed significantly between MCAO and sham groups, as well as between ipsilateral and contralateral sides.
Conclusions:
- The attenuation of cardiovascular responses during static muscle contraction following MCAO is partly attributed to decreased nNOS in the ipsilateral RVLM and increased nNOS in the ipsilateral CVLM.
- nNOS expression within the ventrolateral medulla plays a crucial role in mediating cardiovascular responses during exercise under both normal and pathophysiological conditions.
- These findings highlight the complex role of nNOS in cardiovascular regulation after stroke.
