Kainic acid injections

Intracerebroventricular injection of kainic acid has been shown to result in a well-characterized pattern of neuronal cell damage. In the hippocampus, kainic acid causes a selective lesion of the CA3 pyramidal neurons, an area rich in KA1 and GluR6 receptors. The lesion does not compromise passing axons, which is why this type of (excitotoxic) lesion is often referred to as axon-sparing . Kainic acid injection into the hippocampus also leads to epileptiform discharges in cells normally innervated by the damaged pyramidal neurons. 

Cavalheiro EA, Riche DA, Le Gal La Salle GL. Long-term effects of intrahippocampal kainic acid injection is rats a method for inducing spontaneous recurrent seizures. Electroencephalogr Clin Neurophysiol 1982 53 581-589. 

Ballarin, M., Emfors, P., Linderfors, N. and Persson, H. (1991) Hippocampal damage and kainic acid injection induce a rapid increase in mRNA for BDNF and NGF in the rat brain. Exp. Neurol. 114 35-43. 

Palacios J M, Wamsley J K. and Kuhar M J (1981c) GABA, benzodiazepine, and histamine-Hi receptors in the guinea pig cerebellum effects of kainic acid injections studied by autoradiographic methods. Brain Res 214, 155-162... 

Histologic analysis from a variety of approaches have provided compelling evidence of the axon-sparing effects of kainic acid injected... 

Bird, S. J., Gulley, R. L., Wenthold, R. J., and Fex, J., 1978, Kainic acid injections result in degeneration of cochlear nucleus cells innervated by the auditory nerve. Science 202 1087-1089. 

Fonnum, F., and Walaas, I., 1978, The effect of intrahippocampal kainic acid injections and surgical lesions on neurotransmitters in hippocampus and septum, J. Neurochem. 31 1173-1181. 

Minneman, K. P., Quik, M., and Emson, P., 1978, Receptor-linked cyclic AMP systems in rat neostriatum differential localization revealed by kainic acid injection. Brain Res. 151 507-521. 

Partial seizure activity can be induced by the localised application of chemicals such as cobalt or alumina to the cortex or the injection of chemicals such as PTZ or kainic acid directly into particular brain areas like the hippocampus. 

We recently showed that the iontophoretic injection of kainic acid (a glutamate agonist) in the SLD excites the PS-on neurons and induces a PS-like state (Boissard et al, 2002). Furthermore, the PS-like state induced by bicuculline iontophoresis in the SLD is reversed by the application of kynurenate, a... 

Hippocampal CuZnSOD mRNA levels are increased after systemic injection of kainate at 7 days after injection. The increased mRNA levels correlated with increased specific activities of the enzyme. The CA1 and CA3 neurons lost their CuZnSOD-like immunoreactivity whereas glial cells showed intense immunoreactivity at 3 and 7 days after KA (Kim et al., 2000a,b). Overexpression of CuZnSOD did not protect against OGD- or kainic-acid-induced toxicity in vivo. On... 

McGeer EG, McGeer PL (1976) Duplication of biochemical changes of Huntington s chorea by intras-triatal injections of glutamic and kainic acids. Nature 263 517-519. 

Krammer EB (1980) Anterograde and transsynaptic degeneration en cascade in basal ganglia induced by intrastriatal injection of kainic acid an animal analogue of Huntington s disease. Brain Res 796(1) 209-221. 

FIGURE 42.2. Photomicrographs of mouse hippocampi with pyramidal neurons from the CAl hippocampal area of hrains 1 h after saline (control) and kainic acid (KA, 1 nmol/5 pi, i.c.v.) injections. Treatment with KA induced degeneration of hippocampal dendritic system and a decrease in total length of dendrite and spine density of hippocampal pyramidal neurons. 

Stanley, B. G., L. H. Ha, L. C. Spears and M. G. Dee, 2nd (1993). Lateral hypothalamic injections of glutamate, kainic acid, D,L-alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid or N-methyl-D-aspartic acid rapidly elicit intense transient eating in rats. Brain Res 613(1) 88-95. 

It has recently been discovered that some of the excitant amino acids and their analogues, such as kainlc acid, are nerve cell toxins. That is, when administered to immature animals, either glutamate or aspartate causes degeneration of retinal and hypothalamic cells and, when injected into brain, kainic acid causes irreversible destruction of virtually all neuronal cell bodies around the injection site. These discoveries may be of immense importance N CH2 CH(NH2) COOH with respect to understanding the etiology... 

Application of kainic acid, and the more specific quinolinic acid, into the striatum is followed by Huntington-like structural and biochemical changes excitotoxin injection into the striatum produces locomotor hyperactivity and deficits in learning tests (DiFiglia, 1990). 

Because of its extreme potency and commercial availability, kainic acid has been the excitotoxin most widely used for producing localized lesions in the mammalian central nervous system. While most studies indicate that in situ injection of kainic acid is an effective means of selectively destroying most neuronal perikarya in the vicinity of the injection site, it has become increasingly apparent that the effects of this agent are complex, variable, and often indirect. In order to appreciate the specificity, selectivity, and variability of neuronal vulnerability to locally injected kainic acid, the effects of this agent in two well-characterized brain regions will be reviewed. 

Co-injection of glutamic acid with kainic acid, neither of which are neurotoxic in the decorticate striatum, partially restores kainate s neurotoxicity in this region (Biziere and Coyle, 1979). The essential role of these cortical afferents in the neurotoxic action of kainate has been conclusively established in tissue culture. Explants of striatum cultured alone are insensitive to the neurotoxic effects of kainic acid however, when the striatum is co-cultured with cortical explants resulting in the development of cortical innervation of the striatum, kainate added to the culture medium is effective in lesioning the striatal neurons (Pannula, 1980 Whetsell et al, 1979). 

While most studies have focused on the acute and subacute neurotoxic effects of kainic acid within the straitum, one must also consider the longterm consequences of the excitotoxin lesion. Neurochemical and histologic analysis of the striatum nine months after in situ kainate injection has revealed a profound atrophy of the region congruent with the loss of the... 

---