The dorsal midbrain anticonvulsant zone—I. Effects of locally administered excitatory amino acids or bicuculline on maximal electroshock seizures

Shehab, Safa; Simkins, M.; Dean, Paul; Redgrave, Peter

doi:10.1016/0306-4522(94)00515-7

Cited by 36 publications

(37 citation statements)

References 25 publications

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“…The anterior thalamus (Hodaie et al, 2002), centromedian thalamus (Fisher et al, 1992), substantia nigra pars reticulata (Moshe 1997), and dorsal midbrain anticonvulsant zone (Shehab et al, 1995) have all been proposed as key nodes in the endogenous anticonvulsant circuitry, where an external stimulus can be applied to activate this circuit and suppress seizures. Wilder and Schmidt (1965) observed a strikingly similar pattern with subdural and depth electrode studies in epileptic monkeys.…”

Section: Discussionmentioning

confidence: 99%

Abruptly Attenuated Terminal Ictal Pattern in Pediatrics

Kim¹,

Kuroda²,

Nordli³

2006

Journal of Clinical Neurophysiology

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Section: Discussionmentioning

confidence: 99%

Abruptly Attenuated Terminal Ictal Pattern in Pediatrics

Kim¹,

Kuroda²,

Nordli³

2006

Journal of Clinical Neurophysiology

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“…This statistic varies, from negative values (where the drug THE is longer than the saline THE) to 100% in cases where THE was completely abolished following drug injection. (ii) In accordance with previous practice (Shehab et al, 1995b(Shehab et al, ,c, 1996, THE suppression of < 50% was conservatively classified as 'unprotected' while suppression scores of ‡ 50% were classified as 'protected'. (iii) A particular behavioural characteristic (e.g.…”

Section: Discussionmentioning

confidence: 95%

“…2). In accordance with our previous work (Redgrave et al, 1992b;Shehab et al, 1995bShehab et al, ,c, 1997, an infusion pump was used to deliver a standard injection volume of 400 nL per side over 50 s. Different groups of animals were used to determine the following outcomes:…”

Section: Testing Proceduresmentioning

confidence: 99%

“…However, because of the limitation of three MES tests per subject imposed by our regulatory authorities, it was necessary to use separate groups of animals to answer different questions. Thus, to establish a dose-response relationship for bicuculline, each subject was tested with our standard 100 pmol dose of bicuculline (Shehab et al, 1995b(Shehab et al, ,c, 1997Niemi-Junkola et al, 1997), saline control injections and one other dose of the drug (50 or 200 pmol). Despite this restriction, a clear dose-response relationship was demonstrated in which the 50 pmol provided less protection than the 100 pmol dose, and the 200 pmol dose appeared to be effective over a larger region in the vmRMF than 100 pmol.…”

Section: Technical Considerationsmentioning

confidence: 99%

“…Furthermore, as in previous cases (Redgrave et al, 1992b;Shehab et al, 1995bShehab et al, ,c, 1996Niemi-Junkola et al, 1997;Shehab et al, 1997) the anticonvulsant effects of injected chemical agents often occurred in close association with the activation of locomotor behaviour, we also made qualitative assessments of the behavioural consequences of the pharmacological manipulations of the vmMRF.…”

Section: Introductionmentioning

confidence: 97%

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Pharmacological evidence for an anticonvulsant relay in the rat ventromedial medulla

Shehab¹,

Alzigali²,

Madathil³

et al. 2007

Eur J of Neuroscience

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Local disinhibition of several interconnected regions in the brainstem of rats, including the dorsal midbrain, the mesencephalic locomotor region and the ventrolateral pontine reticular formation, has anticonvulsant properties in the maximal electroshock model of epilepsy. A recent anatomical study [Shehab, S., McGonigle, D., Hughes, D., Todd, A. & Redgrave, P. (2005) Eur. J. Neurosci., 22, 1431-1444.] revealed significant anatomical connections between an anticonvulsant relay region in the ventrolateral pons and reticulospinal projection neurons in the ventromedial medullary reticular formation. This pathway was shown to have both glutamatergic and GABAergic components. The purpose of the present study was to test whether local excitation or inhibition directed to the target zone of this projection in the ventral medulla would also have anticonvulsant properties. Neural excitation induced by local bilateral injections of the GABA(A) antagonist bicuculline into the ventromedial medulla caused a reliable dose-related suppression of hindlimb extension in the maximal electroshock test. The anticonvulsant effect of bicuculline was significantly greater in the terminal zone of the afferent projection from the ventral pons than that observed in adjacent tissue. Neither direct excitation following injections of N-methyl-D-aspartate nor direct inhibition by injections of the GABA agonist muscimol into the same region had reliable anticonvulsant effects. A statistically reliable association was observed between the anticonvulsant and locomotor activation effects of injections of bicuculline into the ventral medulla. No such relationship was found with bicuculline-induced disturbances of muscle tone, as reflected by the presence of postural dysfunction. Together these data establish the final functional link connecting brainstem anticonvulsant circuitry with reticulospinal systems controlling hindlimb musculature.

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