strychnine and Brain-Injuries

Topics: Animals; Anticonvulsants; Biological Assay; Brain Injuries; Diagnosis; Electroconvulsive Therapy; Electroshock; Humans; Methionine Sulfoximine; Methods; Pentylenetetrazole; Phenobarbital; Phenytoin; Picrotoxin; Seizures; Strychnine; Thiosemicarbazones; Trimethadione; Urea

This study was designed to evaluate the neuroprotective effect of l-serine and the underlying mechanisms in mice after traumatic brain injury (TBI) induced using a weight drop model. The mice were intraperitoneally injected with l-serine 3 h after TBI and then injected twice each day for 7 days or until the end of the experiment. The neurological severity score, brain water content, lesion volume, and neurone loss were determined. The levels of TNF-α, IL-1β, IL-6, and IL-10 and the number of GFAP- and Iba-1-positive cells and activated caspase-3-positive neurones in the brain tissue ipsilateral to TBI were also measured. Simultaneously, the influences of l-serine on these variables were observed. In addition, the expression of glycine receptors and l-serine-induced currents were measured. We found l-serine treatment: 1) decreased the neurological deficit score, brain water content, lesion volume, and neurone loss; 2) inhibited activated caspase-3; and 3) reduced the levels of TNF-α, IL-1β and IL-6 and the number of GFAP- and Iba-1-positive cells. The effects of l-serine were antagonised by the administration of strychnine, an antagonist of glycine receptors. In addition, we found that glycine receptors were expressed mainly in the cortical neurones but less in the astrocytes or microglial cells, and l-serine activated these receptors and induced strychnine-sensitive currents in these neurones. In conclusion, l-serine induces the activation of glycine receptors, which alleviates neuronal excitotoxicity, a secondary brain injury process, thereby reduces the activation of astrocytes and microglial cells and secretion of proinflammatory cytokines and inhibits neuronal apoptosis. Thus, l-serine treatment leads to neuroprotection of brain tissue through reducing inflammatory responses and improves recovery of the neurological functions in mice after traumatic brain injury.

Topics: Animals; Apoptosis; Astrocytes; Brain; Brain Edema; Brain Injuries; Cytokines; Disease Models, Animal; Glycine Agents; Mice, Inbred ICR; Microglia; Neuroimmunomodulation; Neurons; Neuroprotection; Neuroprotective Agents; Random Allocation; Receptors, Glycine; Serine; Strychnine

It was shown in experiments on cats that a lesion of the medial forebrain bundle (MFB) and partly of the preoptic region (RPO) at the side of local strychnine application of the cortex (g. suprasylvius medius) resulted in depression of the epileptiform activity in the strychnine-induced focus, as well as in the second "mirror" focus appearing in the symmetrical cortical area of the other hemisphere. This effect could also be obtained under conditions of injury of the MFB alone. The lesion of the MFB and partly of the RPO at the side of the "Mirror" focus leads to depression of the spike potentials in this focus only and does not influence the activity in the primary epileptiform focus. The described effects are considered from the aspect of conceptions of the role played by the determinant dispatch station (DDS) in the central nervous system activity: the primary epileptiform focus plays the role of the hyperactive DDS which induces the development of the secondary foci and maintaines and determines the character of their activity. The results of these studies suggest the participation of the MFB in the modulation of the epileptiform activity in the cortex.

Topics: Action Potentials; Animals; Brain Injuries; Cats; Cerebral Cortex; Epilepsies, Partial; Hypothalamus; Medial Forebrain Bundle; Neural Pathways; Preoptic Area; Strychnine