Evaluation of the microvasculature and cerebral ischemia after experimental subarachnoid hemorrhage in dogs

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Object. Whether cerebral vasospasm occurs only in surface vessels or also in parenchymal arterioles is debatable. The present study was undertaken to evaluate comprehensively the microvasculature of the brainstem after experimental subarachnoid hemorrhage (SAH).

Methods. Nine mongrel dogs of either sex, each weighing between 18 and 24 kg, underwent double blood injections spaced 48 hours apart; the injections were infused into the cisterna magna immediately after angiography of the basilar arteries (BAs). Three additional dogs assigned to a control group received no blood injections. The dogs were killed on Day 7. Axial sections obtained from the midpontine region of both control dogs and animals subjected to SAH were evaluated with respect to the morphological characteristics of vessels and neurons, and for ultrastructural changes.

Severe vasospasm occurred in the BAs of all dogs subjected to SAH. Nevertheless, in these animals, the luminal areas and vessel perimeter in parenchymal arterioles, but not in parenchymal venules, were observed to have increased when compared with those of control dogs (p < 0.01, t-test). No corrugation of the internal elastic lamina was observed and smooth-muscle and endothelial cells remained normal at the ultrastructural level in the dogs with SAH.

Conclusions. In this model, vasospasm of the BAs did not extend into the region of the pons to affect the intraparenchymal arterioles. Dilation of the parenchymal arterioles might serve as compensation for reduced blood flow. Thus, no neuronal ischemia or infarction resulted in the pontine region of the brain.

Article Information

Address reprint requests to: John H. Zhang, M.D., Ph.D., Department of Neurosurgery, Louisiana State University Health Science Center, 1501 Kings Highway, Shreveport, Louisiana 71130. email: johnzhang3910@yahoo.com.

© AANS, except where prohibited by US copyright law.

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Figures

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    Angiograms obtained in four representative dogs on Day 0 (before blood injection) and on Day 7 (after two injections of blood). Severe vasospasm is observed in all dogs.

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    Upper: Photomicrographs of a BA taken from a dog with SAH, showing the common characteristics of vasospasm: corrugation of the IEL and desquamation of the endothelial cells. Lower: Photomicrographs of a BA taken from a control dog lacking the corrugation and desquamation characteristics. H & E, original magnifications × 100 (left) and × 400 (right).

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    Schematic drawings of the dog brain showing the area and plane of sectioning. Slices were obtained from a coronal section from the pontine region that was cut axially. The measurement of arterioles and venules was made from the same section in each dog to minimize the possible bias that could result from measuring different sections.

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    Bar graphs comparing differences in arterioles between control dogs and dogs with SAH. The results shown are from measurements of 96 arterioles. Bars represent mean measurements of arterioles and whiskers represent SEMs. *p < 0.05, t-test.

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    Bar graphs comparing differences in venules in control dogs and dogs with SAH. The results shown are from measurements of 120 venules. Bars represent mean measurements of venules and whiskers represent SEMs.

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    Transmission electron micrographs of arterioles excised from control dogs (upper) and dogs with SAH (lower). Arterioles taken from dogs show no endothelial or smooth-muscle cell damage and lack corrugation of the IEL. Original magnification × 6000.

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    Photomicrographs of neurons from the pontine region. Neurons and neuropil from dogs with SAH (right) display no morphological damage when compared with control (left). H & E, original magnification × 400.

  • View in gallery

    Photomicrographs of neurons from the pontine region. Neurons and neuropil from dogs with SAH (right) display no morphological damage when compared with controls (left). Cresyl violet, original magnification × 400.

References

1.

Brandt LLjunggren BAndersson KEet al: Individual variations in response of human cerebral arterioles to vasoactive substances, human plasma, and CSF from patients with aneurysmal SAH. J Neurosurg 55:4314371981Brandt L Ljunggren B Andersson KE et al: Individual variations in response of human cerebral arterioles to vasoactive substances human plasma and CSF from patients with aneurysmal SAH. J Neurosurg 55:431–437 1981

2.

Brandt LLjunggren BAndersson KEet al: Vasoconstrictive effects of human post-hemorrhagic cerebrospinal fluid on cat pial arterioles in situ. J Neurosurg 54:3513561981Brandt L Ljunggren B Andersson KE et al: Vasoconstrictive effects of human post-hemorrhagic cerebrospinal fluid on cat pial arterioles in situ. J Neurosurg 54:351–356 1981

3.

Dietrich HHKajita YDacey RG Jr: Local and conducted vasomotor responses in isolated rat cerebral arterioles. Am J Physiol 271:H1109H11161996Dietrich HH Kajita Y Dacey RG Jr: Local and conducted vasomotor responses in isolated rat cerebral arterioles. Am J Physiol 271:H1109–H1116 1996

4.

Fernie JMLamb D: New method for measuring intimal component of pulmonary arteries. J Clin Pathol 38:137413791985Fernie JM Lamb D: New method for measuring intimal component of pulmonary arteries. J Clin Pathol 38:1374–1379 1985

5.

Fernie JMLamb D: A new method for quantitating the medial component of pulmonary arteries. The measurements. Arch Pathol Lab Med 109:1561621985Fernie JM Lamb D: A new method for quantitating the medial component of pulmonary arteries. The measurements. Arch Pathol Lab Med 109:156–162 1985

6.

Fernie JMMcLean ALamb D: New method for quantitating the medial component of pulmonary arteries. Factors affecting the measurements. Arch Pathol Lab Med 109:8438481985Fernie JM McLean A Lamb D: New method for quantitating the medial component of pulmonary arteries. Factors affecting the measurements. Arch Pathol Lab Med 109:843–848 1985

7.

Findlay JM: Current management of aneurysmal subarachnoid hemorrhage guidelines from the Canadian Neurosurgical Society. Can J Neurol Sci 24:1611701997Findlay JM: Current management of aneurysmal subarachnoid hemorrhage guidelines from the Canadian Neurosurgical Society. Can J Neurol Sci 24:161–170 1997

8.

Gibbs JMWise RJLeenders KLet al: Evaluation of cerebral perfusion reserve in patients with carotid-artery occlusion. Lancet 1:3103141984Gibbs JM Wise RJ Leenders KL et al: Evaluation of cerebral perfusion reserve in patients with carotid-artery occlusion. Lancet 1:310–314 1984

9.

Grubb RL JrRaichle MEEichling JOet al: Effects of subarachnoid hemorrhage on cerebral blood volume, blood flow, and oxygen utilization in humans. J Neurosurg 46:4464531977Grubb RL Jr Raichle ME Eichling JO et al: Effects of subarachnoid hemorrhage on cerebral blood volume blood flow and oxygen utilization in humans. J Neurosurg 46:446–453 1977

10.

Harper SLBohlen HGRubin MJ: Arterial and microvascular contributions to cerebral cortical autoregulation in rats. Am J Physiol 246:H17H241984Harper SL Bohlen HG Rubin MJ: Arterial and microvascular contributions to cerebral cortical autoregulation in rats. Am J Physiol 246:H17–H24 1984

11.

Hart MN: Morphometry of brain parenchymal vessels following subarachnoid hemorrhage. Stroke 11:6536551980Hart MN: Morphometry of brain parenchymal vessels following subarachnoid hemorrhage. Stroke 11:653–655 1980

12.

Heistad DDFaraci FM: Gene therapy for cerebral vascular disease. Stroke 27:168816931996Heistad DD Faraci FM: Gene therapy for cerebral vascular disease. Stroke 27:1688–1693 1996

13.

Herz DABaez SShulman K: Pial microcirculation in subarachnoid hemorrhage. Stroke 6:4174241975Herz DA Baez S Shulman K: Pial microcirculation in subarachnoid hemorrhage. Stroke 6:417–424 1975

14.

Hutchings MWeller RO: Anatomical relationships of the pia mater to cerebral blood vessels in man. J Neurosurg 65:3163251986Hutchings M Weller RO: Anatomical relationships of the pia mater to cerebral blood vessels in man. J Neurosurg 65:316–325 1986

15.

Jakobsen MOvergaard JMarcussen Eet al: Relation between angiographic cerebral vasospasm and regional CBF in patients with SAH. Acta Neurol Scand 82:1091151990Jakobsen M Overgaard J Marcussen E et al: Relation between angiographic cerebral vasospasm and regional CBF in patients with SAH. Acta Neurol Scand 82:109–115 1990

16.

Johshita HKassell NFSasaki Tet al: Impaired capillary perfusion and brain edema following experimental subarachnoid hemorrhage: a morphometric study. J Neurosurg 73:4104171990Johshita H Kassell NF Sasaki T et al: Impaired capillary perfusion and brain edema following experimental subarachnoid hemorrhage: a morphometric study. J Neurosurg 73:410–417 1990

17.

Kajita YDietrich HHDacey RG Jr: Effects of oxyhemoglobin on local and propagated vasodilatory responses induced by adenosine, adenosine diphosphate, and adenosine triphosphate in rat cerebral arterioles. J Neurosurg 85:9089161996Kajita Y Dietrich HH Dacey RG Jr: Effects of oxyhemoglobin on local and propagated vasodilatory responses induced by adenosine adenosine diphosphate and adenosine triphosphate in rat cerebral arterioles. J Neurosurg 85:908–916 1996

18.

Kassell NFHaley EC JrApperson-Hansen Cet al: Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand. J Neurosurg 84:2212281996Kassell NF Haley EC Jr Apperson-Hansen C et al: Randomized double-blind vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe Australia and New Zealand. J Neurosurg 84:221–228 1996

19.

Kassell NFSasaki TColohan ARet al: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 16:5625721985Kassell NF Sasaki T Colohan AR et al: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 16:562–572 1985

20.

Katusic ZSMilde JHCosentino Fet al: Subarachnoid hemorrhage and endothelial L-arginine pathway in small brain stem arteries in dogs. Stroke 24:3923991993Katusic ZS Milde JH Cosentino F et al: Subarachnoid hemorrhage and endothelial L-arginine pathway in small brain stem arteries in dogs. Stroke 24:392–399 1993

21.

Kim ILeinweber BDMorgalla Met al: Thin and thick filament regulation of contractility in experimental cerebral vasospasm. Neurosurgery 46:4404472000Kim I Leinweber BD Morgalla M et al: Thin and thick filament regulation of contractility in experimental cerebral vasospasm. Neurosurgery 46:440–447 2000

22.

Kontos HAWei EPNavari RMet al: Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 234:H371H3831978Kontos HA Wei EP Navari RM et al: Responses of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 234:H371–H383 1978

23.

Krahn V: The pia mater at the site of the entry of blood vessels into the central nervous system. Anat Embryol 164:2572631982Krahn V: The pia mater at the site of the entry of blood vessels into the central nervous system. Anat Embryol 164:257–263 1982

24.

Krasnoperov RAGrachev SVGerasimov AN: Morphometry error due to non-perpendicular section of microvessel characterized by two-dimensional isotropic arrangement. Bull Exp Biol Med 130:102410262000Krasnoperov RA Grachev SV Gerasimov AN: Morphometry error due to non-perpendicular section of microvessel characterized by two-dimensional isotropic arrangement. Bull Exp Biol Med 130:1024–1026 2000

25.

Lanzino GKassell NFGermanson TPet al: Age and outcome after aneurysmal subarachnoid hemorrhage: why do older patients fare worse? J Neurosurg 85:4104181996Lanzino G Kassell NF Germanson TP et al: Age and outcome after aneurysmal subarachnoid hemorrhage: why do older patients fare worse? J Neurosurg 85:410–418 1996

26.

Martin WRBaker RPGrubb RLet al: Cerebral blood volume, blood flow, and oxygen metabolism in cerebral ischaemia and subarachnoid haemorrhage: an in-vivo study using positron emission tomography. Acta Neurochir 70:391984Martin WR Baker RP Grubb RL et al: Cerebral blood volume blood flow and oxygen metabolism in cerebral ischaemia and subarachnoid haemorrhage: an in-vivo study using positron emission tomography. Acta Neurochir 70:3–9 1984

27.

Mayberg MR: Cerebral vasospasm. Neurosurg Clin N Am 9:6156271998Mayberg MR: Cerebral vasospasm. Neurosurg Clin N Am 9:615–627 1998

28.

Mayhan WGFaraci FMBaumbach GLet al: Effects of aging on responses of cerebral arterioles. Am J Physiol 258:H1138H11431990Mayhan WG Faraci FM Baumbach GL et al: Effects of aging on responses of cerebral arterioles. Am J Physiol 258:H1138–H1143 1990

29.

Megyesi JFVollrath BCook DAet al: In vivo animal models of cerebral vasospasm: a review. Neurosurgery 46:4484612000Megyesi JF Vollrath B Cook DA et al: In vivo animal models of cerebral vasospasm: a review. Neurosurgery 46:448–461 2000

30.

Miyagi YCarpenter RCMeguro Tet al: Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage. J Neurosurg 93:4714762000Miyagi Y Carpenter RC Meguro T et al: Upregulation of rho A and rho kinase messenger RNAs in the basilar artery of a rat model of subarachnoid hemorrhage. J Neurosurg 93:471–476 2000

31.

Nagai HKatsumata TOhya Met al: Effect of subarachnoid haemorrhage on micro-circulation in hypothalamus and brain stem of dogs. Neurochirurgia 19:1351441976Nagai H Katsumata T Ohya M et al: Effect of subarachnoid haemorrhage on micro-circulation in hypothalamus and brain stem of dogs. Neurochirurgia 19:135–144 1976

32.

Nakajima MDate ITakahashi Ket al: Effects of aging on cerebral vasospasm after subarachnoid hemorrhage in rabbits. Stroke 32:6206282001Nakajima M Date I Takahashi K et al: Effects of aging on cerebral vasospasm after subarachnoid hemorrhage in rabbits. Stroke 32:620–628 2001

33.

Ogihara KZubkov AYBernanke DHet al: Oxyhemoglobin-induced apoptosis in cultured endothelial cells. J Neurosurg 91:4594651999Ogihara K Zubkov AY Bernanke DH et al: Oxyhemoglobin-induced apoptosis in cultured endothelial cells. J Neurosurg 91:459–465 1999

34.

Ohkuma HItoh KShibata Set al: Morphological changes of intraparenchymal arterioles after experimental subarachnoid hemorrhage in dogs. Neurosurgery 41:2302361997Ohkuma H Itoh K Shibata S et al: Morphological changes of intraparenchymal arterioles after experimental subarachnoid hemorrhage in dogs. Neurosurgery 41:230–236 1997

35.

Ohkuma HManabe HTanaka Met al: Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke 31:162116272000Ohkuma H Manabe H Tanaka M et al: Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke 31:1621–1627 2000

36.

Ohkuma HSuzuki S: Histological dissociation between intra- and extraparenchymal portion of perforating small arteries after experimental subarachnoid hemorrhage in dogs. Acta Neuropathol 98:3743821999Ohkuma H Suzuki S: Histological dissociation between intra- and extraparenchymal portion of perforating small arteries after experimental subarachnoid hemorrhage in dogs. Acta Neuropathol 98:374–382 1999

37.

Powers WJ: Cerebral hemodynamics in ischemic cerebrovascular disease. Ann Neurol 29:2312401991Powers WJ: Cerebral hemodynamics in ischemic cerebrovascular disease. Ann Neurol 29:231–240 1991

38.

Sobey CGFaraci FM: Subarachnoid haemorrhage: what happens to the cerebral arteries? Clin Exp Pharmacol Physiol 25:8678761998Sobey CG Faraci FM: Subarachnoid haemorrhage: what happens to the cerebral arteries? Clin Exp Pharmacol Physiol 25:867–876 1998

39.

Takayasu MDacey RG Jr: Spontaneous tone of cerebral parenchymal arterioles: a role in cerebral hyperemic phenomena. J Neurosurg 71:7117171989Takayasu M Dacey RG Jr: Spontaneous tone of cerebral parenchymal arterioles: a role in cerebral hyperemic phenomena. J Neurosurg 71:711–717 1989

40.

Takayasu MKajita YSuzuki Yet al: Oxyhemoglobin enhancement of vasopressin-induced constriction in rat cerebral arterioles. Life Sci 56:PL123PL1271995Takayasu M Kajita Y Suzuki Y et al: Oxyhemoglobin enhancement of vasopressin-induced constriction in rat cerebral arterioles. Life Sci 56:PL123–PL127 1995

41.

Tibbs RZubkov AAoki Ket al: Effects of mitogen-activated protein kinase inhibitors on cerebral vasospasm in a double-hemorrhage model in dogs. J Neurosurg 93:104110472000Tibbs R Zubkov A Aoki K et al: Effects of mitogen-activated protein kinase inhibitors on cerebral vasospasm in a double-hemorrhage model in dogs. J Neurosurg 93:1041–1047 2000

42.

Trojanowski T: Early effects of experimental arterial subarachnoid haemorrhage on the cerebral circulation. Part II: Regional cerebral blood flow and cerebral microcirculation after experimental subarachnoid haemorrhage. Acta Neurochir 72:2412551984Trojanowski T: Early effects of experimental arterial subarachnoid haemorrhage on the cerebral circulation. Part II: Regional cerebral blood flow and cerebral microcirculation after experimental subarachnoid haemorrhage. Acta Neurochir 72:241–255 1984

43.

Varsos VGLiszczak TMHan DHet al: Delayed cerebral vasospasm is not reversible by aminophylline, nifedipine, or papaverine in a “two-hemorrhage” canine model. J Neurosurg 58:11171983Varsos VG Liszczak TM Han DH et al: Delayed cerebral vasospasm is not reversible by aminophylline nifedipine or papaverine in a “two-hemorrhage” canine model. J Neurosurg 58:11–17 1983

44.

Vollmer DGTakayasu MDacey RG Jr: An in vitro comparative study of conducting vessels and penetrating arterioles after experimental subarachnoid hemorrhage in the rabbit. J Neurosurg 77:1131191992Vollmer DG Takayasu M Dacey RG Jr: An in vitro comparative study of conducting vessels and penetrating arterioles after experimental subarachnoid hemorrhage in the rabbit. J Neurosurg 77:113–119 1992

45.

Weir BMacdonald RLStoodley M: Etiology of cerebral vasospasm. Acta Neurochir Suppl 72:27461999Weir B Macdonald RL Stoodley M: Etiology of cerebral vasospasm. Acta Neurochir Suppl 72:27–46 1999

46.

Wiernsperger NSchulz UGygax P: Physiological and morphometric analysis of the microcirculation of the cerebral cortex under acute vasospasm. Stroke 12:6246271981Wiernsperger N Schulz U Gygax P: Physiological and morphometric analysis of the microcirculation of the cerebral cortex under acute vasospasm. Stroke 12:624–627 1981

47.

Zabramski JSpetzler RFBonstelle C: Chronic cerebral vasospasm: effect of calcium antagonists. Neurosurgery 18:1291351986Zabramski J Spetzler RF Bonstelle C: Chronic cerebral vasospasm: effect of calcium antagonists. Neurosurgery 18:129–135 1986

48.

Zhang HWeir BMarton LSet al: Mechanisms of hemolysate-induced [Ca2+]i elevation in cerebral smooth muscle cells. Am J Physiol 269:H1874H18901995Zhang H Weir B Marton LS et al: Mechanisms of hemolysate-induced [Ca2+]i elevation in cerebral smooth muscle cells. Am J Physiol 269:H1874–H1890 1995

49.

Zubkov AYLewis AIScalzo D: Transluminal angioplasty and intra-arterial papaverine for the treatment of cerebral vasospasm after ruptured arteriovenous malformations. Surg Neurol 51:75801999Zubkov AY Lewis AI Scalzo D: Transluminal angioplasty and intra-arterial papaverine for the treatment of cerebral vasospasm after ruptured arteriovenous malformations. Surg Neurol 51:75–80 1999

50.

Zubkov AYTibbs REAoki Ket al: Morphological changes of cerebral penetrating arteries in a canine double hemorrhage model. Surg Neurol 54:2122202000Zubkov AY Tibbs RE Aoki K et al: Morphological changes of cerebral penetrating arteries in a canine double hemorrhage model. Surg Neurol 54:212–220 2000

51.

Zubkov AYTibbs REAoki Ket al: Prevention of vasospasm in penetrating arteries with MAPK inhibitors in dog double-hemorrhage model. Surg Neurol 54:2212282000Zubkov AY Tibbs RE Aoki K et al: Prevention of vasospasm in penetrating arteries with MAPK inhibitors in dog double-hemorrhage model. Surg Neurol 54:221–228 2000

52.

Zuccarello MBoccaletti RRomano Aet al: Endothelin B receptor antagonists attenuate subarachnoid hemorrhage-induced cerebral vasospasm. Stroke 29:192419291998Zuccarello M Boccaletti R Romano A et al: Endothelin B receptor antagonists attenuate subarachnoid hemorrhage-induced cerebral vasospasm. Stroke 29:1924–1929 1998

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