JNK Inhibition Potentiates Neurorehabilitative Outcomes Induced by Hypercapnic Hypoxia

Chekulaeva P. A., Zembatova G. M.,  Namiotb G. M., Ignatyukc M. A., Berdnikovb A. K., Kovrizhinad A. R., Kulikove V. P.  and Treguba P. P. 
Journal of Evolutionary Biochemistry and Physiology, 2026, Vol. 62, No. 2, pp. 322–333 DOI: 10.1134/S0022093026020031
In this study, we evaluated the possibility of potentiating the neurorehabilitation effect of hypercapnic hypoxia (HyperH) by the JNK (c-Jun-N-terminal kinase) inhibitor IQ-1 (11H-indeno[1,2- b]quinoxalin-11-one oxime) after photochemically induced cerebral thrombosis in rats. Forty male Wistar rats were divided into 4 equal groups (n = 10), which underwent a course of respiratory HyperH exposures for 30 min a day, 15 sessions: (1) HyperH group (PO2 ≈ 90 mm Hg, PCO2 ≈ 50 mm Hg); (2) HyperH + IQ-1 group; (3) Con (control) group; (4) Soc (sham-operated control) comparison group. After completion of the rehabilitation course, HyperH-exposed animals showed a two-fold reduction in infarct volume compared to the Con group, and an improvement in motor-coordination functions. Combining HyperH with IQ-1 administration enhanced HyperH efficacy only in terms of restoring motor functions (assessed in the rotarod test) and reducing the serum concentration of neuron-specific enolase (NSE). The obtained data indicate that isolated HyperH exposure exerts a pronounced neurorehabilitation effect after focal ischemic injury (p < 0.05). However, combining respiratory training with the JNK blocker IQ-1 shows only a partial potential for enhancing the neurorehabilitation effect of HyperH, which may be due to the delayed blocker administration.