Skip to main content
SpringerLink
Log in
Book cover

Emerging Strategies in Neuroprotection pp 273–288Cite as

Birkhäuser

Insulin, Hypoglycemia, and Ischemic Neuroprotection

  • Chapter
  • First Online:

  • 31 Accesses

Part of the book series: Advances in Neuroprotection ((AN,volume 22))

Abstract

Hypoglycemia, if profound, may give rise to cerebral EEG isoelectricity [blood glucose levels < 1.4 mM, but usually < 1 mM in controlled experimental studies (Auer et al., 1984a)]. EEG silence is the harbinger of a series of biochemical events leading to hypoglycemic brain damage (Siesjö, 1988), structurally manifest as neuronal death (Auer et al., 1984b). Since hypoglycemia is one of the major effects of insulin administration, the very suggestion of the use of insulin in the possible treatment of cerebral ischemia may understandably be viewed with initial skepticism.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Albrecht J, Wróblewska B, Mossakowski M (1982): The binding of insulin to cerebral capillaries and astrocytes of the rat. Neurochem Res 7: 489–494

    Article  CAS  Google Scholar 

  • Araujo DM, Lapchak PA, Collier B, Chabot J-G, Quirion R (1989): Insulin-like growth factor-1 (somatomedin-C) receptors in the rat brain: Distribution and interaction with the hippocampal cholinergic system. Brain Res 484: 130–138

    Article  CAS  Google Scholar 

  • Auer RN, Olsson Y, Siesjö BK (1984a): Hypoglycemic brain injury in the rat: Correlation of density of brain damage with the EEG isoelectric time: A quantitative study. Diabetes 33: 1090–1098

    Article  CAS  Google Scholar 

  • Auer RN, Wieloch T, Olsson Y, Siesjö BK (1984b): The distribution of hypoglycemic brain damage. Acta Neuropathol (Berl) 64: 177–191

    Article  CAS  Google Scholar 

  • Auer RN, Hall P, Ingvar M, Siesjö BK (1986): Hypotension as a complication of hypoglycemia leads to enhanced energy failure but no increase in neuronal necrosis. Stroke 17: 442–449

    Article  CAS  Google Scholar 

  • Auer RN (1986): Hypoglycemic brain damage. Stroke 17: 488–496

    Article  Google Scholar 

  • Blomqvist P, Lindvall O, Wieloch T (1985): Lesions of the locus coeruleus system aggravate ischemic damage in the rat brain. Neurosci Lett 58: 353–358

    Article  CAS  Google Scholar 

  • Bouhaddi K, Thomopoulos P, Fages C, Khelil M, Tardy M (1988): Insulin effect on GABA uptake in astroglial primary cultures. Neurochem Res 13: 1119–1124

    Article  CAS  Google Scholar 

  • Calhoun CL, Mottaz JH (1966): Capillary bed of the rat cerebral cortex: The fine structure in experimental cerebral infarction. Arch Neurol 15: 320–328

    Article  CAS  Google Scholar 

  • Carpenter DO, Briggs DB (1986): Insulin excites neurons of the area postrema and causes emesis. Neurosci Lett 68: 85–89

    Article  CAS  Google Scholar 

  • Duffy KR, Pardridge WM (1987): Blood-brain barrier transcytosis of insulin in developing rabbits. Brain Res 420: 32–38

    Article  CAS  Google Scholar 

  • Frank HJL, Pardridge WM (1981): A direct in vitro demonstration of insulin binding to isolated brain microvessels. Diabetes 30: 757–761

    Article  CAS  Google Scholar 

  • Fukuoka S, Yeh H-S, Mandybur TI, Tew JM Jr (1989): Effect of insulin on acute experimental cerebral ischemia in gerbils. Stroke 20: 396–399

    Article  CAS  Google Scholar 

  • Gjedde A, Hansen AJ, Siemkowicz E (1980): Rapid simultaneous determination of regional blood flow and blood-brain glucose transfer in brain of rat. Acta Physiol Scand 108: 321–330

    Article  CAS  Google Scholar 

  • Grunstein HS, James DE, Storlien LH, Smythe GA, Kraegen EW (1985): Hyperinsulinemia suppresses glucose utilization in specific brain regions: In vivo studies using the euglycemic clamp in the rat. Endocrinology 116: 604–610

    Article  CAS  Google Scholar 

  • Hill JM, Lesniak MA, Pert CB, Roth J (1986): Autoradiographic localization of insulin receptors in rat brain: Prominence in olfactory and limbic areas. Neuroscience 17: 1127–1138

    Article  CAS  Google Scholar 

  • Hill JM, Lesniak MA, Pert CB (1988): Co-localization of IGF-II receptors, IL-1 receptors and thy 1.1 in rat brain. Peptides 9 (Suppl 1):91–96

    Article  Google Scholar 

  • Ito U, Spatz M, Walker JT Jr, Klatzo I (1975): Experimental cerebral ischemia in Mongolian gerbils. I. Light microscopic observations. Acta Neuropathol (Berl) 32: 209–223

    Article  CAS  Google Scholar 

  • Kirino T (1982): Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239: 57–69

    Article  CAS  Google Scholar 

  • Kirino T, Tamura A, Tomukai N, Sano K (1986): Treatable ischemic neuronal damage in the gerbil hippocampus. No To Shinkei 38: 1157–1163

    CAS  PubMed  Google Scholar 

  • Koide T, Wieloch TW, Siesjö BK (1986): Circulating catecholamines modulate ischemic brain damage. J Cereb Blood Flow Metab 6: 559–565

    Article  CAS  Google Scholar 

  • Kraig RP, Petito CK, Plum F, Pulsinelli WA (1987): Hydrogen ions kill brain at concentrations reached in ischemia. J Cereb Blood Flow Metabol 7: 379–386

    Article  CAS  Google Scholar 

  • Kraig RP, Chesler M (1990): Astrocytic acidosis in hyperglycemic and complete ischemia. J Cerebr Blood Flow Metab 10: 104–114

    Article  CAS  Google Scholar 

  • Krumholz A, Stern BJ, Weiss HD (1988): Outcome from coma after cardiopulmo- nary resuscitation: Relation to seizures and myoclonus. Neurology 38: 401–405

    Article  CAS  Google Scholar 

  • LeMay DR, Gehua L, Zelenock GB, D’Alecy G (1988a): Insulin administration protects neurologic function in cerebral ischemia in rats. Stroke 19: 1411–1419

    Article  CAS  Google Scholar 

  • LeMay DR, Lu AC, Zelenock GB, D’Alecy LG (1988b): Insulin administration protects from paraplegia in the rat aortic occlusion model. J Surg Res 44: 352–358

    Article  CAS  Google Scholar 

  • Longstreth W Jr, Inui TS (1984): High blood glucose level on hospital admission and poor neurological recovery after cardiac arrest. Ann Neurol 15: 59–63

    Article  Google Scholar 

  • Longstreth WT Jr, Diehr P, Cobb LA, Hanson RW, Blair AD (1986): Neurologic outcome and blood glucose levels during out-of-hospital cardiopulmonary resuscitation. Neurology 36: 1186–1191

    Article  Google Scholar 

  • Lucignani G, Namba H, Nehlig A, Porrino LJ, Kennedy C, Sokoloff L (1987): Effects of insulin on local cerebral glucose utilization in the rat. J Cereb Blood Flow Metab 7: 309–314

    Article  CAS  Google Scholar 

  • Margolis R, Altszuler N (1967): Insulin in the cerebrospinal fluid. Nature 215: 1375–1376

    Article  ADS  CAS  Google Scholar 

  • Masters BA, Shemer J, Judkins JH, Clarke DW, Le Roith D, Raizada MK (1987): Insulin receptors and insulin action in dissociated brain cells. Brain Res 417: 247–256

    Article  CAS  Google Scholar 

  • McCaleb M, Myers RD, Singer G, Willis G (1979): Hypothalamic norepinephrine in the rat during feeding and push-pull perfusion with glucose, 2-DG, or insulin. Am J Physiol 236: R312–321

    CAS  PubMed  Google Scholar 

  • Meyer JS, Portnoy HD (1958): Localized cerebral hypoglycemia simulating stroke. Neurology 8: 601–614

    Article  CAS  Google Scholar 

  • Myers RE (1979): Lactic acid accumulation as a cause of brain edema and cerebral necrosis resulting from oxygen deprivation. Advan Perinatal Neurol pp 85–114

    Google Scholar 

  • Myers RE, Yamaguchi S (1977): Nervous system effects of cardiac arrest in monkeys. Arch Neurol 34: 65–74

    Article  CAS  Google Scholar 

  • Palovcik RA, Phillips MI, Kappy MS, Raizada MK (1984): Insulin inhibits pyramidal neurons in hippocampal slices. Brain Res 309: 187–191

    Article  CAS  Google Scholar 

  • Rehncrona S, Rosén I, Siesjö BK (1981): Brain lactic acidosis and ischemic cell damage. I. Biochemistry and neurophysiology. J Cereb Blood Flow Metab 1: 297–311

    Article  CAS  Google Scholar 

  • Robertson CS, Grossman RG (1987): Protection against spinal cord ischemia with insulin-induced hypoglycemia. J Neurosurg 67: 739–744

    Article  CAS  Google Scholar 

  • Rothman SM, Olney JW (1986): Glutamate and the pathophysiology of hypoxic/ ischemic brain damage. Ann Neurol 19: 105–111

    Article  CAS  Google Scholar 

  • Salter CF, Chiodo LA (1980): Glucose suppresses basal firing and haloperidolinduced increases in the firing rate of central dopaminergic neurons. Science 210: 1269–1271

    Article  ADS  Google Scholar 

  • Shiu RPC, Paterson JA (1988): Characterization of insulin-like growth factor II peptides secreted by explants of neonatal brain and of adult pituitary from rats. Endocrinology 123: 1456–1460

    Article  CAS  Google Scholar 

  • Siemkowicz E, Hansen AJ, Gjedde A (1982): Hyperglycemic ischemia of rat brain: The effect of post-ischemic insulin on metabolic rate. Brain Res 243: 386–390

    Article  CAS  Google Scholar 

  • Siesjö BK, Ingvar M, Pelligrino D (1983): Regional differences in vascular auto-regulation in the rat brain in severe insulin-induced hypoglycemia. J Cereb Blood Flow Metab 3: 478–485

    Article  Google Scholar 

  • Siesjö BK (1988): Hypoglycemia, brain metabolism, and brain damage. Diabetes/ Metab Rev 4: 113–141

    Article  Google Scholar 

  • Stahl W (1986): The Na,K-ATPase of nervous tissue. Neurochem Int 8:449–476

    Article  CAS  Google Scholar 

  • Sternau LL, Lust WD, Ricci AJ, Ratcheson R (1989): Role for -y-aminobutyric acid in selective vulnerability in gerbils. Stroke 20: 281–287

    Article  CAS  Google Scholar 

  • Strong Ai, Miller SA, West IC (1985): Protection of respiration of a crude mitochondrial preparation in cerebral ischaemia by control of blood glucose. J Neurol Neurosurg Psychiatry 48: 450–454

    Article  CAS  Google Scholar 

  • Strong AJ, Fairfield JE, Monteiro E, Kirby M, Hogg AR, Snape M, Ross-Field L (1990): Insulin protects cognitive function in experimental stroke. J Neurol Neurosurg Psychiatry 53: 847–853

    Article  CAS  Google Scholar 

  • Voll CL, Auer RN (1988): The effect of post-ischemic blood glucose levels on the density and distribution of ischemic brain damage in the rat. Ann Neurol 24: 638–646

    Article  CAS  Google Scholar 

  • Voll CL, Whishaw IQ, Auer RN (1989): Postischemic insulin reduces spatial learning deficit following transient forebrain ischemia in the rat. Stroke 20: 646–651

    Article  CAS  Google Scholar 

  • Voll CL, Auer RN (1991a): Postischemic seizures and necrotizing ischemic brain damage: Neuroprotective effect of postischemic diazepam and insulin. Neurology 41: 423–428

    Article  CAS  Google Scholar 

  • Voll CL, Auer RN (1991b): Insulin attenuates ischemic brain damage independent of its hypoglycemic effect. J Cerebr Blood Flow Metab 11: 1006–1014

    Article  CAS  Google Scholar 

  • Wallum BJ, Taborsky GJ Jr, Porte D Jr, Figlewicz DP, Jacobson L, Beard JC, Ward WK, Dorsa D (1987): Cerebrospinal fluid insulin levels increase during intravenous insulin infusions in man. J Clin Endocrinol Metab 64: 190–194

    Article  CAS  Google Scholar 

  • Werther GA, Hogg A, Oldfield BJ, McKinley MJ, Figdor R, Allen AM, Mendelsohn FAO (1987): Localization and characterization of insulin receptors in rat brain and pituitary gland using in vitro autoradiography and computerized densitometry. Endocrinology 121: 1562–1570

    Article  CAS  Google Scholar 

  • Whishaw IQ (1985): Formation of a place learning-set in the rat: A new procedure for neurobehavioral studies. Physiol Behav 35: 139–143

    Article  CAS  Google Scholar 

  • Young GB, Gilbert JJ, Zochodne DW (1990): The significance of myoclonic status epilepticus in postanoxic coma. Neurology 40: 1843–1848

    Article  CAS  Google Scholar 

Download references

Authors
  1. Roland N. Auer
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. NeuroTherapeutics Corp. and Center for Neurologic Study, 11211 Sorrento Valley Road, 92121, San Diego, CA, USA

    Paul J. Marangos

  2. Department of Pharmacology, Texas College of Osteopathic Medicine, 3500 Camp Bowie Boulevard, 76107, Fort Worth, TX, USA

    Harbans Lal

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Birkhäuser Boston

About this chapter

Cite this chapter

Auer, R.N. (1992). Insulin, Hypoglycemia, and Ischemic Neuroprotection. In: Marangos, P.J., Lal, H. (eds) Emerging Strategies in Neuroprotection. Advances in Neuroprotection, vol 22. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4684-6796-3_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-6796-3_14

  • Published:

  • Publisher Name: Birkhäuser, Boston, MA

  • Print ISBN: 978-1-4684-6798-7

  • Online ISBN: 978-1-4684-6796-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation