Abstract
The putative beneficial role of an early decompression of injured CNS tissue following trauma remains controversial. In this study, we approach this scientific query using a standardized injury of the optic nerve in adult rats. Adult Sprague–Dawley rats were subjected to a standardized optic nerve constriction injury by applying a loose ligature around the nerve for 5 min, 1, 6 or 24 h. All animals were sacrificed at 28 dpi. Viable axons distal to the injury were quantified using semithin sections, and regenerative fibers were studied using antisera to neurofilament and GAP43. Axonal degeneration and glial scar development were analyzed using Fluoro-Jade staining and anti-GFAP, respectively. Visual function was studied with visual evoked potentials (VEP). No significant differences were observed between 1 and 6 h of optic nerve compression. However, the number of viable axons analyzed with neurofilament and on semithin sections, decreased significantly between 6 and 24 h, paralleled by an increase in Fluoro-Jade labeled axonal debris (P < 0.001). GFAP-IR density was significantly higher (P < 0.001) in the 24 h compression group in comparison to 6 h. VEP showed preserved, but impaired visual function in animals subjected to compression up to 6 h, compared to an abolished cortical response at 24 h. Regenerative GAP43-positive sprouts were occasionally found distal to the lesion in animals subjected to compression up to 6 h, but not at 24 h. These findings suggest that early optic nerve decompression within hours after the initial trauma is beneficial for functional outcome.
Similar content being viewed by others
References
AANS/CNS (2002) Guidlines for the management of acute cervical spine and spinal cord injuries. Neurosurgery 50(Suppl):S7–S17
Bellander BM, von Holst H, Fredman P, Svensson M (1996) Activation of the complement cascade and increase of clusterin in the brain following a cortical contusion in the adult rat. J Neurosurg 85:468–475
Bellander BM, Singhrao SK, Ohlsson M, Mattsson P, Svensson M (2001) Complement activation in the human brain after traumatic head injury. J Neurotrauma 18:1295–1311
Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings M, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL Jr, Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR, Young W (1997) Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the third national acute spinal cord injury randomized controlled trial. National acute spinal cord injury study. Jama 277:1597–1604
Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings MG, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL Jr, Piepmeier J, Sonntag VK, Wagner F, Wilberger JE, Winn HR, Young W (1998) Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up. Results of the third national acute spinal cord injury randomized controlled trial. J Neurosurg 89:699–706
Brecknell JE, Fawcett JW (1996) Axonal regeneration. Biol Rev Camb Philos Soc 71:227–255
Cajal SRY (1928) Degeneration and regeneration of the nervous system. RM May, London
Campbell G, Holt JK, Shotton HR, Anderson PN, Bavetta S, Lieberman AR (1999) Spontaneous axonal regeneration after optic nerve injury in adult rat. Neuroreport 10:3955–3960
Davies SJ, Fitch MT, Memberg SP, Hall AK, Raisman G, Silver J (1997) Regeneration of adult axons in white matter tracts of the central nervous system. Nature 390:680–683
Dezawa M, Kawana K, Negishi H, Adachi-Usami E (1999) Glial cells in degenerating and regenerating optic nerve of the adult rat. Brain Res Bull 48:573–579
Dimar JR II, Glassman SD, Raque GH, Zhang YP, Shields CB (1999) The influence of spinal canal narrowing and timing of decompression on neurologic recovery after spinal cord contusion in a rat model. Spine 24:1623–1633
Doster SK, Lozano AM, Aguayo AJ, Willard MB (1991) Expression of the growth-associated protein GAP-43 in adult rat retinal ganglion cells following axon injury. Neuron 6:635–647
Fawcett JW, Asher RA (1999) The glial scar and central nervous system repair. Brain Res Bull 49:377–391
Fehlings MG, Tator CH (1999) An evidence-based review of decompressive surgery in acute spinal cord injury: rationale, indications, and timing based on experimental and clinical studies. J Neurosurg 91:1–11
Fischer D, Heiduschka P, Thanos S (2001) Lens-injury-stimulated axonal regeneration throughout the optic pathway of adult rats. Exp Neurol 172:257–272
Foerster AP, Holmes MJ (1999) Spontaneous regeneration of severed optic axons restores mapped visual responses to the adult rat superior colliculus. Eur J Neurosci 11:3151–3166
Forrester J, Peters A (1967) Nerve fibres in optic nerve of rat. Nature 214:245–247
Frank M, Wolburg H (1996) Cellular reactions at the lesion site after crushing of the rat optic nerve. Glia 16:227–240
Gasque P, Neal JW, Singhrao SK, McGreal EP, Dean YD, Van BJ, Morgan BP (2002) Roles of the complement system in human neurodegenerative disorders: pro-inflammatory and tissue remodeling activities. Mol Neurobiol 25:1–17
Gellrich NC, Gellrich MM, Zerfowski M, Eufinger H, Eysel UT (1997) Clinical and experimental study of traumatic optic nerve damage. Ophthalmologe 94:807–814
Gellrich NC, Schimming R, Zerfowski M, Eysel UT (2002) Quantification of histological changes after calibrated crush of the intraorbital optic nerve in rats. Br J Ophthalmol 86:233–237
Greenberg MS (1997) Handbook of neurosurgery. Greenberg Graphics, Inc., Lakeland
Guest J, Eleraky MA, Apostolides PJ, Dickman CA, Sonntag VK (2002) Traumatic central cord syndrome: results of surgical management. J Neurosurg 97:25–32
Gunnarsson T, Fehlings MG (2003) Acute neurosurgical management of traumatic brain injury and spinal cord injury. Curr Opin Neurol 16:717–723
Heiduschka P, Fischer D, Thanos S (2005) Recovery of visual evoked potentials after regeneration of cut retinal ganglion cell axons within the ascending visual pathway in adult rats. Restor Neurol Neurosci 23:303–312
Huber AB, Schwab ME (2000) Nogo-A, a potent inhibitor of neurite outgrowth and regeneration. Biol Chem 381:407–419
Ide C (1996) Peripheral nerve regeneration. Neurosci Res 25:101–121
Lazarov-Spiegler O, Solomon AS, Zeev-Brann AB, Hirschberg DL, Lavie V, Schwartz M (1996) Transplantation of activated macrophages overcomes central nervous system regrowth failure. Faseb J 10:1296–1302
Levin LA, Joseph MP, Rizzo JF III, Lessell S (1994) Optic canal decompression in indirect optic nerve trauma. Ophthalmology 101:566–569
Levin LA, Beck RW, Joseph MP, Seiff S, Kraker R (1999) The treatment of traumatic optic neuropathy: the International Optic Nerve Trauma Study. Ophthalmology 106:1268–1277
Lindå H, Piehl F, Dagerlind A, Verge VM, Arvidsson U, Cullheim S, Risling M, Ulfhake B, Hokfelt T (1992) Expression of GAP-43 mRNA in the adult mammalian spinal cord under normal conditions and after different types of lesions, with special reference to motoneurons. Exp Brain Res 91:284–295
MacLaren RE (1998) Regeneration and transplantation of the optic nerve: developing a clinical strategy. Br J Ophthalmol 82:577–583
MacLaren RE (1999) Re-establishment of visual circuitry after optic nerve regeneration. Eye 13:277–284
Mattsson P, Morgan BP, Svensson M (1998) Complement activation and CD59 expression in the motor facial nucleus following intracranial transection of the facial nerve in the adult rat. J Neuroimmunol 91:180–189
Monsul NT, Geisendorfer AR, Han PJ, Banik R, Pearse ME, Skolasky RL Jr, Hoffman PN (2004) Intraocular injection of dibuturyl cyclic AMP promotes axon regeneration in rat optic nerve. Exp Neurol 186:124–133
Ohlsson M, Bellander B-M, Langmoen IA, Svensson M (2003) Complement activation following optic nerve crush in the adult rat. Journal of Neurotrauma 20:895–904
Ohlsson M, Mattsson P, Svensson M (2004a) A temporal study of axonal degeneration and glial scar formation following a standardized crush injury of the optic nerve in the adult rat. Restor Neurol Neurosci 22:1–10
Ohlsson M, Mattsson P, Wamil BD, Hellerqvist CG, Svensson M (2004b) Macrophage stimulation using a group B-streptococcus exotoxin (CM101) leads to axonal regrowth in the injured optic nerve. Restor Neurol Neurosci 22:33–41
Ohlsson M, Westerlund U, Langmoen IA, Svensson M (2004c) Methylprednisolone treatment does not influence axonal regeneration or degeneration following optic nerve injury in the adult rat. J Neuro-Ophthalmol 24:11–18
Olson L (2002) Medicine: clearing a path for nerve growth. Nature 416:589–590
Paxinos G (1995) The rat nervous system. Academic Press, San Diego
Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, San Diego
Podhajsky RJ, Bidanset DJ, Caterson B, Blight AR (1997) A quantitative immunohistochemical study of the cellular response to crush injury in optic nerve. Exp Neurol 143:153–161
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 751:37–46
Thakar A, Mahapatra AK, Tandon DA (2003) Delayed optic nerve decompression for indirect optic nerve injury. Laryngoscope 113:112–119
Thanos S, Naskar R, Heiduschka P (1997) Regenerating ganglion cell axons in the adult rat establish retinofugal topography and restore visual function. Exp Brain Res 114:483–491
Ueda Y, Walker SA, Povlishock JT (2006) Perivascular nerve damage in the cerebral circulation following traumatic brain injury. Acta Neuropathol (Berl) 112:85–94
Wohlrab TM, Maas S, de Carpentier JP (2002) Surgical decompression in traumatic optic neuropathy. Acta Ophthalmol Scand 80:287–293
Yang WG, Chen CT, Tsay PK, de Villa GH, Tsai YJ, Chen YR (2004) Outcome for traumatic optic neuropathy—surgical versus nonsurgical treatment. Ann Plast Surg 52:36–42
Yoles E, Muller S, Schwartz M (1997) NMDA-receptor antagonist protects neurons from secondary degeneration after partial optic nerve crush. J Neurotrauma 14:665–675
Acknowledgments
We gratefully acknowledge Mrs. Britt Meijer for excellent technical assistance and the Swedish Medical Research Council and Karolinska Institutet for funding.
Author information
Authors and Affiliations
Corresponding author
Additional information
Funding: Grants from Swedish Medical Research Council and Karolinska Institutet. Disclosure statement: No disclosure to be stated for the two authors.
Rights and permissions
About this article
Cite this article
Ohlsson, M., Svensson, M. Early decompression of the injured optic nerve reduces axonal degeneration and improves functional outcome in the adult rat. Exp Brain Res 179, 121–130 (2007). https://doi.org/10.1007/s00221-006-0775-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00221-006-0775-1