Skip to main content
SpringerLink
Log in

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

  • Published:
Pediatric Radiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Levy SR, Abroms IF, Marshall PC, Rosquete EE (1985) Seizures and cerebral infarction in the full term newborn. Ann Neurol 17: 366–370

    Article  PubMed  Google Scholar 

  2. Barmada MA, Moossy J, Shuman RM (1979) Cerebral infarcts with arterial occlusion in neonates. Ann Neurol 6: 495–502

    PubMed  Google Scholar 

  3. Ment LR, Duncan CC, Ehrenkranz RA (1984) Perinatal cerebral infarction. Ann Neurol 16: 559–568

    Article  PubMed  Google Scholar 

  4. Klesh KW, Murphy TF, Scher MS, Buchanan DE, Maxwell EP, Guthrie RD (1987) Cerebral infarction in persistent pulmonary hypertension of the newborn. AJDC 141: 852–857

    PubMed  Google Scholar 

  5. Cook TM, Crutcher A (1986) Intrahippocampal injection of kainic acid produces significant pyramidal cell loss in neonatal rats. Neuroscience 18: 79–92

    Article  PubMed  Google Scholar 

  6. Hastings MH, Winn P, Dunnett SB (1985) Neurotoxic amino acid lesions of the lateral hypothalamus: a parametric comparison of the effects of ibotinate, N-methyl-D-aspartate and quisqualate in the rat. Brain Res 360: 248–256

    Article  PubMed  Google Scholar 

  7. McDonald MW, Silverstein FS, Johnston MV (1988) Neurotoxicity of N-methyl-D-aspartate is markedly enhanced in developing rat central nervous system. Brain Res 459: 200–203

    Article  PubMed  Google Scholar 

  8. Young RSK, Petroff OAC, Aquila WJ, Yates J (1991) Effects of glutamate, quisqualate, and N-methyl-D-aspartate in neonatal brain. Exp Neurol 111: 362–368

    Article  PubMed  Google Scholar 

  9. Hernanz-Schulman M, Cohen W, Genieser NB (1988) Sonography of cerebral infarction in infancy. AJR 150: 897–902

    PubMed  Google Scholar 

  10. Hill A, Martin DJ, Daneman A, Fitz CR (1983) Focal ischemic cerebral injury in the newborn: diagnosis by ultrasound and correlation with computed tomographic scan. Pediatrics 71: 790–793

    PubMed  Google Scholar 

  11. Heymann MA, Payne BD, Hoffman JIE, Rudolph AM (1977) Blood flow measurements with radionuclide-labeled particles. Prog cardiovasc Dis 20: 55–77

    PubMed  Google Scholar 

  12. Naidich TP, Yousefzadeh DK, Gusnard DA, Naidich JB (1986) Sonography of the internal capsule and basal ganglia in infants. Part II: Localization of pathologic processes in the sagittal section through the caudothalamic groove. Radiology 161: 615–621

    PubMed  Google Scholar 

  13. Taylor GA, Fitz CR, Kapur S, Short BL (1989) Cerebrovascular accidents ininfants treated with ECMO: sonographic-pathologic correlation. AJR 153: 355–361

    PubMed  Google Scholar 

  14. Taylor GA, Short BL, Walker LK, Traystman RJ (1990) Intracranial blood flow: quantification with duplex Doppler and color Doppler flow US. Radiology 176: 231–236

    PubMed  Google Scholar 

  15. Busija DW, Leffler CW (1989) Dilator effects of amino acid neurotransmitters on piglet pial arterioles. Am J Physiol 257 (Heart Circ Physiol 26): H1200-H1203

    PubMed  Google Scholar 

  16. Beart PM, Sheehan K-AM, Manallack DT (1988) Absence of N-methyl-D-aspartate receptors on ovine cerebral microvessels. J Cereb Blood Flow Metab 8: 879–882

    PubMed  Google Scholar 

  17. Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526

    PubMed  Google Scholar 

  18. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84: 9265–9269

    PubMed  Google Scholar 

  19. Snyder SH, Bredt DS (1991) Nitric oxide as a neuronal messenger. Trends Pharmacol Sci USA 12: 125–128

    Article  Google Scholar 

  20. Garthwaite J, Charles SL, Chess-Williams R (1988) Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger. Nature 336: 385–388

    Article  PubMed  Google Scholar 

  21. Arneric SP, Honig MA, Milner TA, Greco S, Iadecola C, Reis DJ (1988) Neuronal and endothelial sites of acetylcholine synthesis and release associated with microvessels in rat cerebral cortex: ultrastructural and neurochemical studies. Brain Res 454: 11–30

    PubMed  Google Scholar 

  22. Edvinsson L, Mackenzie ET, McCullough J, Uddman R (1987) Perivascular innervation and receptor mechanisms in cerebrovascular bed. In: Wood JH (ed) Cerebral blood flow: physiologic and clinical aspects. McGraw-Hill, New York, pp 145–172

    Google Scholar 

  23. Bosley TM, Rosenquist AC, Kushner M, Burke A, Stein A, Dann R, Cobbs W, Savino PJ, Schatz NJ, Alavi A, Reivich M (1985) Ischemic lesions of occipital cortex and optic radiations: positron emission tomography. Neurology 35: 470–484

    PubMed  Google Scholar 

  24. Celesia GG, Polcyn RE, Holden JE, Nickles RJ, Koeppe RA, Gatley SJ (1984) Determination of regional cerebral blood flow in patients with cerebral infarction. Arch Neurol 41: 262–267

    PubMed  Google Scholar 

  25. Dauth G, Gilman S, Frey KA, Penney JB Jr (1985) Basal ganglia glucose utilization after recent precentral ablation in the monkey. Ann Neurol 17: 431–438

    PubMed  Google Scholar 

  26. Meyer JS, Yamamoto M, Haymen LA, Sakai F, Nakajima S, Armstrong D (1980) Cerebral embolism: local CBF and edema measured by CTR scanning and Xe8 inhalation. Neurol Res 2: 101–120

    PubMed  Google Scholar 

  27. Lenzi GL, Frackowiak RSJ, Jones T (1982) Cerebral oxygen metabolism and blood flow in human cerebral ischemic infarction. J Cereb Blood Flow Metab 2: 321–335

    PubMed  Google Scholar 

  28. Chida K, Iadecola C, Reis DJ (1989) Global reduction in cerebral blood flow and metabolism elicited from intrinsic neurons of fastigial nucleus. Brain Res 500: 177–192

    Article  PubMed  Google Scholar 

  29. Kempinsky WH (1958) Experimental study of distant effects of acute focal brain injury: a study of diaschisis. Arch Neurol Psychiatry 79: 376–389

    Google Scholar 

  30. Meyer JS, Hata T, Imai A (1987) Clinical and experimental studies of diaschisis: In: Wood JH (ed) Cerebral blood flow: physiologic and clinical aspects. McGraw-Hill, New York, pp 481–502

    Google Scholar 

  31. Levy DE, Duffy TE (1977) Cerebral energy metabolism during transient ischemia and recovery in the gerbil. J Neurochem 28: 63–70

    PubMed  Google Scholar 

  32. Nakai M, Iadecola C, Reis DJ (1982) Global cerebral vasodilatation by stimulation of rat fastigial cerebellar nucleus. Am J Physiol 243: H226-H235

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Russell H. Morgan Department of Radiology, The Johns Hopkins Medical Institutions, 600 North Wolfe Street, 21205, Baltimore, Maryland, USA

    G. A. Taylor MD

  2. Department of Pediatrics, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

    G. A. Taylor MD & M. V. Johnston

  3. Department of Neurology, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

    W. A. Trescher & M. V. Johnston

  4. Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA

    R. J. Traystman

  5. The Kennedy-Kreiger Institute, Baltimore, Maryland, USA

    W. A. Trescher & M. V. Johnston

Authors
  1. G. A. Taylor MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. A. Trescher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. J. Traystman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. V. Johnston
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported in part by USPHS NIH grant NS 20020

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taylor, G.A., Trescher, W.A., Traystman, R.J. et al. Acute experimental neuronal injury in the newborn lamb: US characterization and demonstration of hemodynamic effects. Pediatr Radiol 23, 268–275 (1993). https://doi.org/10.1007/BF02010913

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02010913

Keywords

Search

Navigation