Experimental Neuronal Injury in the Newborn Lamb: A Comparison of N-Methyl-D-Aspartic Acid Receptor Blockade and Nitric Oxide Synthesis Inhibition on Lesion Size and Cerebral Hyperemia

Abstract

Vol. 38, No. 5, 1995 Printed in U.S.A.The purpose of this study was to compa re the effects of dizocilipine maleate (MK-801) and W -nitro-L-arginine methyl ester (L-NAME) on focal excitotoxic brain injury and associated hemod ynamic response in the newborn lamb. A 27 gauge needle was placed into the right striatum in 28 anesthetized newborn lambs. Seven animals were placed in each group. A negative control group received 0.2 mL of buffered saline, a positive control group received 5 /Lmol of N-methyl-D-aspartic acid (NMDA) alone, and two groups received NMDA and pretreatment with L-NAME. Ultrasound images and cerebral blood flow determinations (microspheres) were obtained before, and at 20, 40, and 60 min after, intrastrial injection. Three animals in each group underwent histopathologic evaluation. Sonographic lesions were visible immediatel y after intracerebral injection . Saline injection resulted in small lesions (mean volume; 13.6 :t 5 mrrr') without hyperemia. NMDA alone resulted in larger lesions (92.9 :t 24 mrrr') and hyperemia to both hemispheres, whereas pretreatment with MK-801 reduced lesion size (11.7 :t 6 mm") and completely ablated cerebral hyperemia . Pretreatment with L-NAME showed no effect on lesion size (69.9 :t 20 mm") and hyperemia only in the ipsilateral hemisphere. Sonogr aphic lesions correlated well with gross and histopathologic appearance. We concluded that NMDA-induced focal brain injury and associated hyperemia in the newborn lamb appear to be specific NMDA receptor-mediated events. NO production probab ly does not play a major part in NMDA-indu ced neonatal neuronal injury, and may be only partly responsible for regional hyperemia during NMDA injection. (Pediatr Res 38: 644-651 , 1995) Abbr eviations NM DA, N-methyl-D-aspartic acid L-NAME, AP-nitro-L-arginine methyl ester MK-801, dizoci lipine maleate NO, nitric oxide CVR, cerebrovascula r resistance CBF, cerebral blood flow ANOVA, analysis of variance There is considerable evidence now suggesting that glutamate may mediate the neurotoxicity observe d in hypoxicischemic brain injury. Several source s of data support this hypothesis: (i) glutamate produces neurona l injury similar to that observed after cerebra l hypoxia-ischemia; (ii) elevated extracellu lar levels of glutamate and aspartate are present during cerebral ischemia; (iii) excitatory deafferentation results in improved neuronal survival; and (iv) NMDA receptor an-

Optical monitoring of stress-related changes in the brain tissues and vessels associated with hemorrhagic stroke in newborn rats

“…Indeed, LSCI results show the increase in rCBF in venous component of cerebral circulation in the prestroke stage and, in especially, in the post-stroke time. These results are consistent with clinical data suggesting that hyperperfusion is one of the stroke-associated damages of the brain [44][45][46]. Both LSCI and DOCT imaging show the time-depended progressive changes in the sagittal sinus from the initial stage of stroke until the incidence of brain bleeding.…”

Carotid hemodynamic parameters in hemodialysis patients

“…As well, Albayrak et al [29] showed that the cross-sectional area of bilateral ICA and VA and the peak systolic velocity of left ICA increased in patients with hypoxemic, chronic obstructive lung disease. Moreover, it has been reported that hypoxemia caused cerebral vasodilatation via nitric oxide in an experimental study [30]. Clinical reflection of hypoxemia has been shown as decreased RI in asphyxiated babies [31].…”

Nitric Oxide Inhibition after Hypoxia-Ischemia Elevates Pulmonary Arterial Pressure and Increases Oxygen Need

“…Although physiological rapid involution in pulmonary pressure and vascular changes in deed occur after birth, it does not seem very probable that the variation in the postnatal age of the lambs in the different groups [4][5][6][7][8][9][10] might have influenced the findings with re spect to pulmonary pressure. No difference existed between the postnatal age between the three groups.…”

“…Therefore, it has been suggested that re duction of nitric oxide production by inhibi tion of nitric oxide synthesis by NLA may reduce postasphyxial reperfusion injury of the brain [9][10][11]. On the other hand, however, nit ric oxide plays a major role in the regulation of pulmonary vascular tone as well.…”

“…However, recently it has been recognized that upon reperfusion and rcoxygenation as occurs after birth asphyxia, excessive amounts of nitric oxide are pro duced [5,6]. This subsequently leads to neu ronal damage by nitric oxide-mediated exces sive production of glutamate and free radical species, which are, at least partly, responsible for the post-hypoxic-ischemic (HI) reperfu sion damage of brain tissue [5,7], Although results of studies with respect to focal isch emia arc conflicting [6], inhibition of nitric oxide production in the immediate post-Hl period after birth asphyxia has been shown to reduce brain damage in neonatal rats and newborn lambs [8][9][10].…”