Excitotoxic lesions

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. 

Alderson HL, Faulconbridge LF, Gregory LP, Latimer MP, Winn P (2003) Behavioural sensitisation to repeated d-amphetamine effects of excitotoxic lesions of the pedunculopontine tegmental nucleus. Neuroscience 118 311-315... 

The ultradian sleep—wake and temperature rhythm produced by 3rd ventricle infusion of TGFa closely resembles the effect of a focal excitotoxic lesion of SPZ neurons (Lu et al 2001). This ultradian rhythm is normally suppressed by circadian control and is disinhibited when SPZ neurons fail to relay SCN circadian information to sleep—wake circuits. Our results indicate that chronic TGFa administration uncouples SPZ neurons from sleep-regulatory circuits and that SPZ neurons expressing the EGFR transmit circadian information from the SCN to sleep—wake centres, in addition to likely regulating circadian locomotor activity. 

The junction between the MPOA and lateral preoptic areas is the ventral part of the bed nucleus of the stria terminalis (ventral BST), and excitotoxic lesions disrupt retrieval behaviors and other aspects of maternal behavior in postpartum rats (Numan and Numan, 1996). Strong ventral BST projections to the lateral septum, substantia innominata, PVN, VTA, periaque-dutal gray matter, retrorubral field, and the region surrounding the locus coeruleus (Numan and Numan, 1996). 

Studies of animals with central cholinergic lesions produced by either pharmacological inhibition of choline uptake or direct excitotoxic lesions of basal forebrain cholinergic neurons have shown highly specific attentional deficits (Muir et al. 1992 Robbins et al. 1989). These animals showed deficits that might be predicted from studies of humans with AD that is, they showed increased response latency and increased responsiveness to irrelevant sensory stimuli. Studies by Vidal (1994b) have shown that administration of a nicotinic antagonist into rat prefrontal cortex impairs performance on spatial... 

Hodges H, Sowinski P, Turner JJ, et al Comparison of the effects of the 5-HTj receptor antagonists WAY-100579 and ondansetron on spatial learning in the water maze in rats with excitotoxic lesions of the forebrain chohnergic system. Psychopharmacology 125 146-161, 1996... 

Acarin L., Paris J., Gonzalez B., and Castellano B. (2002). Glial expression of small heat shock proteins following an excitotoxic lesion in the immature rat brain. Glia 38 1-14. 

Hantraye P, Riche D, Maziere M, Isacson O (1990) A primate model of Huntington s disease behavioral and anatomical studies of unilateral excitotoxic lesions of the caudate-putamen in the baboon. Exp Neurol 108 91-104. 

Excitotoxic lesions generated in primates using NMDA receptor agonists such as quinolinic acid cause neuronal loss similar to that found in HD, emphasizing, the potential role of excitotoxicity in HD. Intrastriatal injections of the reversible succinate dehydrogenase inhibitor, malonate, into rats caused a decrease in ATP levels and increased lactate and excitotoxic lesions, which could be prevented by NMDA antagonists. 

Dias R, Robbins TW, Roberts AC. Primate analogue of the Wisoconsin Card Sorting Test effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav Neurosci 1996 110 872-886. 

Phillips JM, Latimer MP, Gupta S, Winn P, Brown VJ (1998) Excitotoxic lesions of the subthalamic nucleus ameliorate asymmetry induced by striatal dopamine depletion in the rat. Behav Brain Res 90 73-77. 

Alderson HL, Parkinson JA, Robbins TW, Everitt BJ (2001) The effects of excitotoxic lesions of the nucleus accumbens core or shell regions on intravenous heroin self-administration in rats. Psychopharmacology 255 455-463. 

Jongen-Relo AL, Feldon J (2002) Specific neuronal protein a new tool for histological evaluation of excitotoxic lesions. Physiol Behav 75(4-5) 449-456. 

Maldonado-Irizarry CS, Kelley AE (1995) Excitotoxic lesions of the core and shell subregions of the nucleus accumbens differentially disrupt body weight regulation and motor activity in rat. Brain Res Bull 38(6) 551 559. 

Collins P, Roberts AC, Dias R, Everitt BJ, Robbins TW (1998) Perseveration and strategy in a novel spatial self-ordered sequencing task for nonhuman primates Effects of excitotoxic lesions and DA depletions of the prefrontal cortex. J Cogn Neurosci 70 332-354. 

Evenden JL, Marston HM, Jones GH, Giardini V, Lenard L, Everitt BJ, Robbins TW (1989) Effects of excitotoxic lesions of the substantia innominata, ventral and dorsal globus pallidus on visual discrimination, acquisition, performance and reversal in the rat. Behav Brain Res 32 129-149. 

Beal MF, Brouillet E, Jenkins BG, Ferrante RJ, Kowal NW, Miller JM, Storey E, Srivastava R, Rosen BR, Hyman BT (1993) Neurochemical and histologic char acterization of striatal excitotoxic lesions produced by tire mitochondrial toxin 3-nitr opropionic acid. JNeurosci 13 4181 182. 

Roberts, A.C., Robbins, T.W., Everitt, B.J. and Muir, J.L. 1992. A specific form of cognitive rigidity following excitotoxic lesions of the basal forebrain in marmosets. Neuroscience, 47 251-264. 

Brouillet EP, Shinobu L, McGarvey U, et al. 1993. Manganese injection into the rat striatum produces excitotoxic lesions by impairing energy metabolism. Exp Neurol 120 89-94. 

Storey E, Hyman BT, Jenkins B, et al. 1992. l-MethyM-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism. J Neurochem 58 1975-1978. 

Beal, M.F., E. Brouillet, B.G. Jenkins, R.J. Ferrante, N.W. Kowall, J.M. Miller, E. Storey, R. Srivastava, B.R. Rosen, and B.T. Hyman (1993). Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J Neurosci 13(10) 4181 192. 

Monkeys Cynomolgous 4.0 mg/kg (i.p.) Chewing with frothing gagging and vomiting, abnormal movements,tremors excitotoxic lesions in CNS [103]... 

HistopathologicaUy, the response of nonhuman primates is also comparable to both rodent and human patients. Excitotoxic lesions consisting of vacuolation of the neutrophil, astrocytic swelling, and neuronal shrinkage and hyperchromasia were detected in the area postrema, the hypothalamus, the hippocampus, and the inner layers of the retina in monkeys given domoic acid [103,104,119,120]. 

Oral administration of 1 % creatine to male Sprague-Dawley rats significantly attenuated striatal excitotoxic lesions produced by N-methyl-D-aspartate, but had no effect on lesions produced by a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or kainic acid (Malcon et al. 2000). 

Maikova, L., Gaffan, D., and Murray, E. A. 1997. Excitotoxic lesions of the amygdala fail to produce impairment in visual learning for auditory secondary reinforcement but iuter-fere with reinforcer devaluation effects in rhesus monkeys. Journal of Neuroscience, 17(15), 6011-6020. 

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