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Temporal changes in physiological and molecular markers in various brain regions following transient global ischemia in rats

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Abstract

Several mechanisms are involved in the loss of cellular integrity and tissue destructions in various brain regions during ischemic insult. The affected brain employs various self-repair mechanisms during the poststroke recovery. Therefore, the current study involves time course changes in different brain regions following ischemia in terms of inflammation, oxidative stress and apoptosis for which a bilateral common carotid arteries occlusion model was chosen. The development of oxidative stress was seen with a marked increase in ROS and NO levels with concomitant decrease in GSH levels and also the activities of anti-oxidant enzymes. These alterations were accompanied with decreased levels of neurotransmitters and motor and cognitive deficits at various time points. Increased expressions of various pro-inflammatory cytokines and a decline in BDNF levels in hippocampal regions on 7th day post ischemia, suggesting their role in its pathogenesis. The restoration of BDNF and neurotransmitter levels along with significant decline in inflammatory cytokine levels 14th day onwards following ischemia in hippocampus suggested poststroke recovery. The extent of neuronal damage was found to be increased significantly on 7th day post ischemia as indicated by TUNEL assay and hematoxylin and eosin staining depicting enhanced number of pyknotic neurons in cortical and hippocampal regions. Cortical regions of the ischemic brains were severely affected while hippocampal regions showed significant poststroke recovery, which might attributed to the normalization of BDNF and pro-inflammatory cytokine levels. In conclusion, the present study established the central role of BDNF and pro-inflammatory cytokines in the poststroke recovery. Also, the cortical and hippocampal regions were found to be more susceptible for ischemic injury. As our results indicated, full recovery after ischemic injury in different brain regions was not achieved, therefore further studies with long-term recovery time are required to be conducted.

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Abbreviations

TGCI:

Transient global cerebral ischemia

ROS/RNS:

Reactive oxygen species/reactive nitrogen species

DA:

Dopamine

NE:

Norepinephrine

5-HT:

Sertonin

DTNB:

5,5′-Dithiobis-(2-nitrobenzoic acid)

TTC:

Triphenyltetrazolium chloride

ECD:

Electrochemical detector

TL:

Transfer latency

BDNF:

Brain derived neurotrophic factor

LSD:

Least significant difference

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Acknowledgements

The study was carried out with the funds provided by Department of Science & Technology/Innovation in Science Pursuit for Inspired Research (DST/INSPIRE), India with IF no. IF130058.

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Authors and Affiliations

  1. Department of Physiology, Armed Forces Medical College, Pune, India

    Monika Kapoor

  2. Department of Biophysics, Panjab University, Chandigarh, India

    Sheetal Sharma & Bimla Nehru

  3. Department of Biochemistry, Panjab University, Chandigarh, India

    Rajat Sandhir

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  1. Monika Kapoor
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Correspondence to Bimla Nehru.

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Kapoor, M., Sharma, S., Sandhir, R. et al. Temporal changes in physiological and molecular markers in various brain regions following transient global ischemia in rats. Mol Biol Rep 46, 6215–6230 (2019). https://doi.org/10.1007/s11033-019-05060-7

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