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Thalidomide protects against cerebral ischemia reperfusion injury: Role of pERK1/2‐NFκB signaling
Author(s) -
Nassar Noha N.,
Mohamed Reham A.,
El-Yamany Mohammed F.,
Abdel Rahman Abdel A.,
Al-Shorbagy Muhammad Y.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03098
Subject(s) - neuroprotection , ischemia , hippocampal formation , reperfusion injury , medicine , pharmacology , neurochemical , neuroscience , tumor necrosis factor alpha , immunology , endocrinology , biology
While thalidomide (TLM) protects against neuronal injury and behavioral deficits caused by cerebral ischemia reperfusion (IR), the mechanisms of TLM neuroprotective effect remain unknown. Here, we tested the hypothesis that suppression of the phospho‐extracellular signal regulated kinase (pERK1/2)‐ nuclear factor kappa (NFκ)‐B signaling, subsequent to tumor necrosis factor‐α (TNF‐α) inhibition, underlies TLM mediated neuroprotection. Male Wistar rats subjected to occlusion of both common carotid arteries for 45 min followed by declipping and allowing reperfusion for 24 h exhibited histopathological damage, memory impairment, motor incoordination and hyperactivity. Unilateral intra‐hippocampal TLM ameliorated these behavioral deficits along with the following ex vivo hippocampal effects: (i) abrogation of the IR‐evoked elevations in hippocampal TNF‐α, pERK1/2, NFκB, MPO, BDNF, iNOS contents and (ii) partial restoration of the reduced anti‐inflammatory cytokine IL‐10 and pS852 nNOS. These neurochemical effects, which were replicated by the pERK1/2 inhibitor PD98059, likely mediate the reductions in c‐Fos and caspase‐3 levels and the ensuing anti‐apoptotic effect of TLM in the IR model. These results substantiate a crucial anti‐inflammatory role for pERK1/2 inhibition in the salutary neuronal and behavioral effects of TLM in a model of IR injury.