Facilitated beam-walking recovery during acute phase by kynurenic acid treatment in a rat model of photochemically induced thrombosis causing focal cerebral ischemia.
We previously demonstrated the presence of activated areas in the non-injured contralateral sensorimotor cortex in addition to the ipsilateral sensorimotor cortex of the area surrounding a brain infarction, using a rat model of focal photochemically induced thrombosis (PIT) and functional magnetic resonance imaging. Using this model, we next applied gene expression profiling to screen key molecules upregulated in the activated area. RNA was extracted from the ipsilateral and contralateral sensorimotor cortex to the focal brain infarction and from the sham controlled cortex, and hybridized to gene-expression profiling arrays containing 1,322 neurology-related genes. Results showed that glycine receptors were upregulated in both the ipsilateral and contralateral cortex to the focal ischemic lesion. To prove the preclinical significance of upregulated glycine receptors, kynurenic acid, an endogenous antagonist to glycine receptors on neuronal cells, was administered intrathecally. As a result, the kynurenic acid significantly improved behavioral recovery within 10 days from paralysis induced by the focal PIT (p < 0.0001), as evaluated with beam walking. These results suggest that intrathecal administration of a glycine receptor antagonist may facilitate behavioral recovery during the acute phase after brain infarction.
Abo
Masahiro
M
Department of Rehabilitation, The Jikei University School of Medicine, Tokyo, Japan.
Yamauchi
Hideki
H
Suzuki
Masahiko
M
Sakuma
Mio
M
Urashima
Mitsuyoshi
M
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D005260:Female; D007839:Functional Laterality; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D007736:Kynurenic Acid / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010777:Photochemistry / Q000379:methods*; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function / Q000187:drug effects; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology; D018709:Statistics, Nonparametric; D013927:Thrombosis / Q000139:chemically induced* / Q000150:complications; D013997:Time Factors; D016138:Walking
D018691:Excitatory Amino Acid Antagonists; D007736:Kynurenic Acid