NF-kappaB inhibition after neonatal cerebral hypoxia-ischemia improves long-term motor and cognitive outcome in rats.
We recently demonstrated that inhibition of the NF-kappaB-pathway by the specific peptide inhibitor TAT-NBD markedly reduced cerebral injury in a rat model of perinatal hypoxic-ischemic (HI) brain damage. The aim of the current study was to assess whether neuroprotection by TAT-NBD is associated with long-term functional improvements after neonatal HI. Postnatal-day 7 rats subjected to HI showed motor deficits in the cylinder rearing test and adhesive removal task. HI-treated animals also showed cognitive impairments in a visuo-spatial learning task (modified hole board) as defined by an increased latency to complete this task and increased numbers of short- and long-term memory errors. HI animals treated with TAT-NBD [20mg/kg i.p.] at 0 and 3h post-HI did not show impairments in the cylinder rearing test, adhesive removal task and modified hole board. In conclusion, the almost complete reduction in lesion size observed after TAT-NBD treatment was associated with long-lasting normalization of sensorimotor and cognitive functions.
Department of Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Michael A
MA
van der Kooij
Cora H
CH
Nijboer
Frauke
F
Ohl
Floris
F
Groenendaal
Cobi J
CJ
Heijnen
Frank
F
van Bel
Annemieke
A
Kavelaars
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects*; D003463:Cues; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009048:Motor Skills / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015398:Signal Transduction
D016328:NF-kappa B