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Perivascular nerve damage in the cerebral circulation following traumatic brain injury

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Abstract

Traumatic brain injury (TBI) causes cerebral vascular dysfunction. Most have assumed that it was the result of endothelial and/or smooth muscle alteration. No consideration, however, has been given to the possibility that the forces of injury may also damage the perivascular nerve network, thereby contributing to the observed abnormalities. To test this premise, we subjected rats to impact acceleration. At 6 h, 24 h and 7 days post-TBI, cerebral basal arteries were removed and processed with antibody targeting protein gene product 9.5 (PGP-9.5), with parallel assessments of 5-hydroxytryptamine (5-HT) accumulation in the perivascular nerves. Additionally, Fluoro-Jade was also used as a marker of axonal degeneration. The perivascular nerve network revealed no abnormality in sham animals. However, by 6 h post injury, Fluoro-Jade reactivity appeared in the perivascular regions, with the number of fibers increasing with time. By 24 h post injury, a significant reduction in the perivascular 5-HT accumulation occurred, together with a reduction in PGP-9.5 fiber staining. At 7 days, a recovery of the PGP-9.5 immunoreactivity occurred, however, it did not reach a control-like distribution. These studies suggest that neurogenic damage occurs following TBI and may be a contributor to some of the associated vascular abnormalities.

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References

  1. Alabadi JA, Torregrosa G, Salom JB, Miranda FJ, Barbera MD, Mayordomo F, Alborch E (1994) Changes in the adrenergic mechanisms of cerebral arteries after subarachnoid hemorrhage in goats. Neurosurgery 34(6):1027–1033

    PubMed  CAS  Google Scholar 

  2. Armstead WM (1997) Brain injury impairs ATP-sensitive K+ channel function in piglet cerebral arteries. Stroke 28(11):2273–2279

    PubMed  CAS  Google Scholar 

  3. Bleys RL, Cowen T (2001) Innervation of cerebral blood vessels: morphology, plasticity, age-related, and Alzheimer’s disease-related neurodegeneration. Microsc Res Tech 53(2):106–118

    Article  PubMed  CAS  Google Scholar 

  4. Bouma GJ, Muizelaar JP (1992) Cerebral blood flow, cerebral blood volume, and cerebrovascular reactivity after severe head injury. J Neurotrauma 9(Suppl 1):S333–S348

    PubMed  Google Scholar 

  5. Busto R, Dietrich WD, Globus MY, Alonso O, Ginsberg MD (1997) Extracellular release of serotonin following fluid-percussion brain injury in rats. J Neurotrauma 14(1):35–42

    PubMed  CAS  Google Scholar 

  6. Chang JY, Ekblad E, Kannisto P, Owman C (1989) Serotonin uptake into cerebrovascular nerve fibers of rat, visualization by immunohistochemistry, disappearance following sympathectomy, and release during electrical stimulation. Brain Res 492(1–2):79–88

    Article  PubMed  CAS  Google Scholar 

  7. Cowen T, Thrasivoulou C (1990) Cerebrovascular nerves in old rats show reduced accumulation of 5-hydroxytryptamine and loss of nerve fibers. Brain Res 513(2):237–243

    Article  PubMed  CAS  Google Scholar 

  8. Edvinsson L, Ekman R, Jansen I, McCulloch J, Mortensen A, Uddman R (1991) Reduced levels of calcitonin gene-related peptide-like immunoreactivity in human brain vessels after subarachnoid haemorrhage. Neurosci Lett 121(1–2):151–154

    Article  PubMed  CAS  Google Scholar 

  9. Edvinsson L, Juul R, Jansen I (1994) Perivascular neuropeptides (NPY, VIP, CGRP and SP) in human brain vessels after subarachnoid haemorrhage. Acta Neurol Scand 90(5):324–330

    Article  PubMed  CAS  Google Scholar 

  10. Engelborghs K, Haseldonckx M, Van Reempts J, Van Rossem K, Wouters L, Borgers M, Verlooy J (2000) Impaired autoregulation of cerebral blood flow in an experimental model of traumatic brain injury. J Neurotrauma 17(8):667–677

    Article  PubMed  CAS  Google Scholar 

  11. Foda MAAE, Marmarou A (1994) A new model of diffuse brain injury in rats. Part II: Morphological characterization. J Neurosurg 80(2):301–313

    PubMed  CAS  Google Scholar 

  12. Goda M, Isono M, Fujiki M, Kobayashi H (2002) Both MK801 and NBQX reduce the neuronal damage after impact-acceleration brain injury. J Neurotrauma 19(11):1445–1456

    Article  PubMed  Google Scholar 

  13. Golding EM (2002) Sequelae following traumatic brain injury. The cerebrovascular perspective. Brain Res Rev 38(3):377–388

    Article  PubMed  Google Scholar 

  14. Hara H, Kobayashi S (1988) Reduced tyrosine hydroxylase-like immunoreactivity around cerebral arteries after experimental subarachnoid hemorrhage in rats. An immunohistochemical study. Acta Neuropathol (Berl) 75(5):538–540

    Article  CAS  Google Scholar 

  15. Hara H, Nosko M, Weir B (1986) Cerebral perivascular nerves in subarachnoid hemorrhage. A histochemical and immunohistochemical study. J Neurosurg 65(4):531–539

    PubMed  CAS  Google Scholar 

  16. Jackowski A, Crockard A, Burnstock G (1989) 5-Hydroxytryptamine demonstrated immunohistochemically in rat cerebrovascular nerves largely represents 5-hydroxytryptamine uptake into sympathetic nerve fibers. Neuroscience 29(2):453–462

    Article  PubMed  CAS  Google Scholar 

  17. Jackowski A, Crockard A, Burnstock G, Lincoln J (1989) Alterations in serotonin and neuropeptide Y content of cerebrovascular sympathetic nerves following experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab 9(3):271–279

    PubMed  CAS  Google Scholar 

  18. Kontos HA, Wei EP (1992) Endothelium-dependent responses after experimental brain injury. J Neurotrauma 9(4):349–354

    Article  PubMed  CAS  Google Scholar 

  19. Kontos HA, Wei EP, Dietrich WD, Navari RM, Povlishock JT, Ghatak NR, Ellis EF, Patterson JL Jr (1981) Mechanism of cerebral arteriolar abnormalities after acute hypertension. Am J Physiol 240(4):H511–H527

    PubMed  CAS  Google Scholar 

  20. Lin WM, Hsieh ST, Huang IT, Griffin JW, Chen WP (1997) Ultrastructural localization and regulation of protein gene product 9.5. Neuroreport 29(14):2999–3004

    Article  Google Scholar 

  21. Lobato RD, Marin J, Salaices M, Burgos J, Rivilla F, Garcia AG (1980) Effect of experimental subarachnoid hemorrhage on the adrenergic innervation of cerebral arteries. J Neurosurg 53(4):477–479

    PubMed  CAS  Google Scholar 

  22. Marmarou A, Foda MAAE, van den Brink W, Campbell J, Kita H, Demetriadou K (1994) A new model of diffuse brain injury in rats. Part I: pathophysiology and biomechanics. J Neurosurg 80(2):291–300

    Article  PubMed  CAS  Google Scholar 

  23. Navarro X, Verdu E, Wendelschafer-Crabb G, Kennedy WR (1997) Immunohistochemical study of skin reinnervation by regenerative axons. J Comp Neurol 380(2):164–174

    Article  PubMed  CAS  Google Scholar 

  24. Pluta RM, Thompson BG, Dawson TM, Snyder SH, Boock RJ, Oldfield EH (1996) Loss of nitric oxide synthase immunoreactivity in cerebral vasospasm. J Neurosurg 84(4):648–654

    Article  PubMed  CAS  Google Scholar 

  25. Povlishock JT, Becker DP, Sullivan HG, Miller JD (1978) Vascular permeability alterations to horseradish peroxidase in experimental brain injury. Brain Res 153(2):223–239

    Article  PubMed  CAS  Google Scholar 

  26. Sandor P (1999) Nervous control of the cerebrovascular system: doubts and facts. Neurochem Int 35(3):237–259

    Article  PubMed  CAS  Google Scholar 

  27. Sato M, Chang E, Igarashi T, Noble LJ (2001) Neuronal injury and loss after traumatic brain injury: time course and regional variability. Brain Res 917(1):45–54

    Article  PubMed  CAS  Google Scholar 

  28. Schmued LC, Albertson C, Slikker W Jr (1997) Fluoro-Jade: a novel fluorochrome for the sensitive and reliable histochemical localization of neuronal degeneration. Brain Res 751(1):37–46

    Article  PubMed  CAS  Google Scholar 

  29. Schmued LC, Hopkins KJ (2000) Fluoro-Jade B: a high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 874(2):123–130

    Article  PubMed  CAS  Google Scholar 

  30. Stone JR, Walker SA, Povlishock JT (1999) The visualization of a new class of traumatically injured axons through the use of a modified method of microwave antigen retrieval. Acta Neuropathol (Berl) 97(4):335–345

    Article  CAS  Google Scholar 

  31. Suehiro E, Wei EP, Ueda Y, Kontos HA, Povlishock JP (2003) The posttraumatic use of hypothermia followed by rapid rewarming results in alterations of the cerebral microcirculation. J Neurotrauma 20(4):381–399

    Article  PubMed  Google Scholar 

  32. Suehiro E, Povlishock JT (2001) Exacerbation of traumatically induced axonal injury by rapid posthypothermic rewarming and attenuation of axonal change by cyclosporin A. J Neurosurg 94(3):493–498

    PubMed  CAS  Google Scholar 

  33. Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rode J (1983) PGP 9.5–a new marker for vertebrate neurons and neuroendocrine cells. Brain Res 278(1–2):224–228

    Article  PubMed  CAS  Google Scholar 

  34. Uemura Y, Sugimoto T, Okamoto S, Handa H, Mizuno N (1987) Changes of neuropeptide immunoreactivity in cerebrovascular nerve fibers after experimentally produced SAH. Immunohistochemical study in the dog. J Neurosurg 66(5):741–747

    Article  PubMed  CAS  Google Scholar 

  35. Wei EP, Dietrich DW, Povlishock JT, Navari RM, Kontos HA (1980) Functional, morphological, and metabolic abnormalities of the cerebral microcirculation after concussive brain injury in cats. Circ Res 46(1):37–47

    PubMed  CAS  Google Scholar 

  36. Wei EP, Kontos HA, Dietrich DW, Povlishock JT, Ellis EF (1981) Inhibition by free radical scavengers and by cyclooxygenase inhibitors of pial arteriolar abnormalities from concussive brain injury in cats. Circ Res 48(1):95–103

    PubMed  CAS  Google Scholar 

  37. Wilkinson KD, Lee KM, Deshpande S, Duerksen-Hughes P, Boss JM, Pohl J (1989) The neuron-specific protein PGP 9.5 is an ubiquitin carboxyl-terminal hydrolase. Science 246(4930):670–673

    Article  PubMed  CAS  Google Scholar 

  38. Yoshioka J, Clower BR, Smith RR (1984) The angiopathy of subarachnoid hemorrhage I. Role of vessel wall catecholamines. Stroke 15(2):288–294

    PubMed  CAS  Google Scholar 

  39. Youn SH, Sakuda M, Kurisu K, Wakisaka S (1997) Regeneration of periodontal primary afferents of the rat incisor following injury of the inferior alveolar nerve with special reference to neuropeptide Y-like immunoreactive primary afferents. Brain Res 752(1–2):161–169

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors wish to thank Thomas Coburn, and Lynn Davis for their skilled technical assistance. Supported by NIIT grant NS 20193

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, Medical College of Virginia Campus of Virginia Commonwealth University, Box 980709, Richmond, VA, 23298-0709, USA

    Yuji Ueda, Susan A. Walker & John T. Povlishock

  2. Department of Neurosurgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, 755-8505, Yamaguchi, Ube, Japan

    Yuji Ueda

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  1. Yuji Ueda
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Correspondence to John T. Povlishock.

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Ueda, Y., Walker, S.A. & Povlishock, J.T. Perivascular nerve damage in the cerebral circulation following traumatic brain injury. Acta Neuropathol 112, 85–94 (2006). https://doi.org/10.1007/s00401-005-0029-5

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  • DOI: https://doi.org/10.1007/s00401-005-0029-5

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