Correlation of changes in the GABA-ergic system with the development of spasticity in paraplegic cats.
Following spinal cord transection there occurred decreases in Km and Vmax of glutamate decarboxylase (GAD) both above and below the lesion, and an initial decrease in the concentration of GABA. Concomitantly, there was a gradual decrease in presynaptic inhibition. Eight to 12 weeks after spinal cord transection, Km and Vmax for GAD returned to control values, but the GABA content of the spinal cord below the lesion increased significantly and presynaptic inhibition became maximally depressed. These results suggested that during the chronic phase of spinal cord injury there is a decrease in release of GABA, the interneuronal inhibitory neurotransmitter which mediates presynaptic inhibition. Diazepam, a GABA enhancer, increased presynaptic inhibition in acute and chronic spinal cats, this being accompanied by a reduction in somatic muscular spasticity. The degree of this enhancement by diazepam, however, is attenuated with gradual loss of presynaptic inhibition. In the acute cat, a conditioning volley applied to cutaneous afferents blocked the inhibition of the monosynaptic response to extensor motoneurones. In contrast, in chronic spinal cats (eight to 12 weeks), the duration of complete blockade was markedly reduced and was followed by a prolonged period which cutaneous nerve stimulation potentiated the monosynaptic discharge. Similar to GABA, there also occurred an increase of substance P below the level of the lesion. Other neurotransmitters (e.g., norepinephrine, serotonin) accumulated above and disappeared below the transection level. Although somatic msucular spasticity appears to be, to some extent, due to GABA dysfunction in the spinal cord, alterations in "normal" functioning of other neurotransmitters and the loss of supraspinal control also contribute to this state.
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D002415:Cats; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007700:Kinetics; D009128:Muscle Spasticity / Q000503:physiopathology; D010264:Paraplegia / Q000503:physiopathology*; D012023:Reflex, Monosynaptic; D013116:Spinal Cord / Q000201:enzymology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase