Blockade of Nitric Oxide Synthesis Inhibits Hippocampal Hyperemia in Kainic Acid-Induced Seizures

Rigaud-Monnet, Anne-Sophie; Pinard, Elisabeth; Borredon, Josiane; Seylaz, Jacques

doi:10.1038/jcbfm.1994.72

Cited by 42 publications

(16 citation statements)

References 43 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Superfusion with NA attenuated the local increases in LCBF, suggesting that the cerebrovasodilation elicited by focal epileptic seizures depends on NO production. Recent studies using systemic injection of NOS inhibitors (35,36) showed a reduction of the reactive hyperemia associated with generalized seizures, but their interpretation is complicated by the generalized vasoconstricValues are means ± SE. *P < 0.05, compared with the contralateral cortex (aCSF perfused) (Student's dependent t test).…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

Vasconcelos¹,

Baldwin²,

Wasterlain³

1995

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The role of nitric oxide (NO) in the increase in local cerebral blood flow (LCBF) elicited by focal cortical epileptic seizures was investigated in anesthetized adult rats. Seizures were induced by topical bicuculline methiodide applied through two cranial windows drilled over homotopic sites of the frontal cortex, and LCBF was measured by quantitative autoradiography by using 4-iodo[N-methyl-14C]antipyrine. Superfusion of an inhibitor of NO synthase, N1"-nitro-L-arginine (NA; 1 mM), for 45 min abolished the increase of LCBF induced by topical bicuculline methiodide (10 mM) [164 ± 18 ml/100 g per min in the artificial cerebrospinal fluid (aCSF)-superfused side and 104 + 12 ml/100 g per ml in the NA-superfused side; P < 0.005]. This effect was reversed by coapplication of an excess of L-arginine substrate (10 mM) (218 ±-22 ml/100 g per min in the aCSF-superfused side and 183 ± 31 ml/100 g per min in the NA + L-Arg-superfused side) but not by 10 mM D-arginine, a stereoisomer with poor affinity for NO synthase (193 ± 17 ml/100 g per min in the aCSF-superfused side and 139 ± 21 ml/100 g per min in the NA + D-Arg-superfused side; P < 0.005). Superfusion of the guanylyl cyclase inhibitor methylene blue attenuated the LCBF increase elicited by topical bicuculline methiodide by 25% ± 16% (P < 0.05). The present findings suggest that NO is the mediator of the vasodilation in response to focal epileptic seizures.Nitric oxide (NO) or a closely related NO-containing compound that is synthesized from L-arginine has been identified as one of the endothelium-derived relaxing factors which modulate vascular responses to various stimuli by activation of soluble guanylyl cyclase (1-3). NO plays an important role in the regulation of the basal cerebral circulation (4-9) and modulates cerebral blood flow during hypercapnia (7,8,10, 11), local neuronal activation (12-16), or activation of intracerebral neural pathways (17, 18). However, NO may not be involved in cerebrovascular responses to stimulation of reticular formation (17), to somatosensory stimulation (19), and to some hypoxic stimuli (5,8, 11). NO has also been suggested to be an important transmitter in the. central nervous system (20-23) and may represent a major mechanism to couple local perfusion with neuronal activity (14,15,24).The mechanisms regulating increases in cerebral blood flow in response to seizures have not been clearly defined, although different substances like HI, C02, K+, prostaglandins, and adenosine might be involved (25)(26)(27).The present experiments were performed to study the role of NO in cerebral vasodilation during focal seizure activity in anesthetized adult rats. NO is synthesized from L-arginine by NO synthase (NOS) (28,29). NOS activity can be inhibited by No-substituted arginine such as Nw-nitro-L-arginine (NA) (3, 30). Furthermore, NO exerts its vasodilating action by acti-The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accorda...

show abstract

Section: Discussionmentioning

confidence: 99%

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

Vasconcelos¹,

Baldwin²,

Wasterlain³

1995

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Recent experimental investigations have shown that NO might meet the essential criterion to function as a retrograde messenger for long term potentiation in hippocampal cells, a process known to be involved in mammalian learning and memory [24]. NO mediates changes in cerebral blood flow under certain physiological [25] and pathological conditions [26,27]. However, excessive production of NO has also been implicated in a number of pathophysiological conditions including stress [28].…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Withania somnifera Dunal.: A Possible Mechanism

2009

View full text Add to dashboard Cite

Present study was carried out to understand the possible mechanism of neuroprotective action of the root extract of Withania somnifera Dunal (WS). The study is focused on WS mediated inhibition of nitric oxide production, which is known to mediate neurodegeneration during stress. Adult mice (28 +/- 5 g) were exposed to restraint stress for 30 days. Activity of NADPH diaphorase (NADPH-d) and factors (Acetylcholine, serotonin and corticosterone), which regulates NADPH-d activity were studied. Treatment with WS extract for 30 days during stress, significantly reversed the stress induced NADPH-d activation. Observations suggest that inhibition of NADPH-d by WS is not a direct effect of extract on NADPH-d, instead it inhibits via suppressing corticosterone release and activating cholineacetyltransferase, which in turn increase serotonin level in hippocampus to inhibit NADPH-d. Together, the main mechanism underlying the neuroprotective effects of WS can be attributed to its role in the down regulation of nNOS and neurochemical alterations of specific neurotransmitter systems. These observations thus suggest that WS root extract could be developed as a potential preventive or therapeutic drug for stress induced neurological disorders.

show abstract

“…injections of either L-NAME (10 mg/kg), L-NAME and L-arg (10 mg/kg and 300 mg/kg, respectively), or 7NI (40 mg/kg). At thesc dose ranges, 7NI and LNAME affect seizure activity, reactive hyperemia, and consequences in various adult rodent models of cpilepsy (24,(29)(30)(31)(32)(33) and, from 30 to 120 min after the injection, produce 50-85% inhibition of brain NOS (3334). The effect of r,-arg alone (300 mg/kg) was studied at 10 min before the first PTZ dose, to compensate for the quite rapid metabolism of L-arg, mainly through the urea cycle.…”

Section: Pharmacologic Treatmentsmentioning

confidence: 99%

Role of Nitric Oxide in Pentylenetetrazol‐Induced Seizures: Age‐Dependent Effects in the Immature Rat

et al. 2000

View full text Add to dashboard Cite

Summary:Purpose: Seizure susceptibility and consequences are highly age dependent. To understand the pathophysiologic mechanisms involved in seizures and their consequences during development, we investigated the role of nitric oxide (NO) in severe pentylenetetrazol (PTZ)-induced seizures in immature rats.Methods: Four cortical electrodes were implanted in 10-dayold (P 10) and 2 I -day-old (P2 I ) rats, and seizures were induced on the following day by repetitive injections of subconvulsive doses of PTZ. The effects of N"-nitro-1.-arginine methyl ester ([,-NAME; 10 mg/kg) and 7-nitroinda~ole (7N1; 40 mglkg), two NO synthase (NOS) inhibitors, and L-arginine (~q ; 300 mgi kg), the NOS substrate, were evaluated regarding the mean PTZ dose, seizure type and duration, and mortality rate.Results: At P10, the postseimre mortality rate increased from 18-29% for the rats receiving PTZ only to 100% and 89% for the rats rccciving L-NAME and 7N1, respectively; whereas Larg had no effect. Conversely, at P21, NOS inhibitors did not affect the 82-89% mortality rate induced by PTZ alone, whereas L-arg decreased the mortality rate to 29%. In addition, all NO-related drugs increased the duration of ictal activity at PIO, whereas at P21, L-arg and L-NAME affected thc first seizure type, producing clonic seizures with L-arg and tonic seizures with 1.-NAME.Conclusions: The relative natural protection of very immature rats (Pl0) against PTZ-induced deaths could be linkcd to a high availability of 1.-arg and, hence, endogenous NO. At P21, the modulation of seizure type by NO-related compounds may he related to the maturation of the brain circuitry, in particular the forebrain, which is involved in the expression of c h i c seizures. Key Words: Nitric oxide synthase inhibition-1.-Arginine-Pentylenetetrazol seizures-Postnatal development-Rat brain.In both humans and experimental models of epilepsy, seizure susceptibility and consequences are highly age dependcnt and change dramatically with postnatal development ( I ,2). Epilepsy is very common in infancy and childhood, with children having a higher propensity to develop severe seizures or status epilepticus than adults (3). In addition, a greater risk of developmental impairment i< associated with early, rather than late, childhood seizure onset (4). Experimental studies have shown that although prolonged seizures can cause brain damage and behavioral impairments in mature rats, very immature rats are considered to be protected against these deleterious effects (1,2,5). However, whereas the question remains whether recurrent or severe seizures are harmful to the developing brain, it has been shown recently that Accepted September 23, 1999. Addrcss corrcspondence and reprinl requests to Dr. A. Pcrcira de Vasconcelos at INSERM U398, Facult6 dc MBdecine, I I rue Humann, 67085 Slrasbourg CCdex, France. E-mail: Pcrcira@Neurochem.U-S tras bg . fr seizures can damage the brain of immature rats, rabbits, and monkeys (6-9).Previous studies from our laboratory have shown that an episode of seve...

show abstract

Blockade of Nitric Oxide Synthesis Inhibits Hippocampal Hyperemia in Kainic Acid-Induced Seizures

Cited by 42 publications

References 43 publications

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.

Neuroprotective Effects of Withania somnifera Dunal.: A Possible Mechanism

Role of Nitric Oxide in Pentylenetetrazol‐Induced Seizures: Age‐Dependent Effects in the Immature Rat

Contact Info

Product

Resources

About