Acute experimental neuronal injury in the newborn lamb: US characterization and demonstration of hemodynamic effects

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Abstract
Background and purpose: Microinjection into the brain with N-methyl-D-aspartate (NMDA), a synthetic analogue of glutamate, has been used as a chemical model of perinatal hypoxic-ischemic injury. Little is known about the sonographic characteristics and hemodynamic consequences of these cytotoxic lesions. An understanding of these features may be useful in the early sonographic identification of stroke in newborns.Methods: Twenty newborn lambs were anesthetized, paralyzed, and mechanically ventilated. Between 0.5 and 5 μ mole NMDA in 0.2 ml phosphate buffered salinen=18), or buffered saline only (n=2) was injected into the right putamen under sonographic guidance. Serial grey-scale and color Doppler images of the brain, Doppler spectra of the middle cerebral and thalamostriate arteries, cerebral blood flow (CBF) determinations using radiolabeled microspheres (n=9), and cerebral oxygen extraction (n=4) were obtained before, and at 15, 60, and 120 min after NMDA injection. Pathologic examination was obtained in 11 animals.Results: Homogeneous, well defined, moderately echogenic lesions surrounded by marked focal hyperemia on color Doppler were identified in every animal injected with 5 μ mole NMDA within minutes of injection. Lesions were characterized by focal areas of chromatolysis and cytoplasmic shrinkage, with scattered petechial hemorrhage. No lesions or hyperemia were observed in the animals injected with normal saline. Mean supratentorial CBF increased from 64±9 ml/min/100 g (control) to 152±30, 115±19, and 102±8 ml/min/100 g at 15, 60, and 120 min after injection respectively. The most marked increases occurred in right midbrain (467% of control), diencephalon (388%), and temporal lobe (282%), but were also observed in homotopic regions of the left hemisphere, and in pons, medulla, and cerebellum. Mean blood flow velocity in the middle cerebral artery, and thalmoperforator artery correlated well with changes in hemispheric and midbrain CBF respectively. (r=0.57–0.74,p=0.0001, andr=0.65–0.67,p=0.0001 respectively).Conclusions: Focal brain lesions may be identified by sonography within minutes after experimentally induced neuronal injury. Alterations in echotexture are primarily due to intracellular cytoplasmic changes and microscopic hemorrhage. Local intracerebral injection of NMDA in newborn lambs increases both local and global CBF.