{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:30:23Z","timestamp":1790242223953,"version":"4.1.0"},"reference-count":52,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:p content-type=\"fine-print\"><jats:italic>Object.<\/jats:italic> Traumatic brain injury (TBI) attenuates the cerebral vasodilation to hypercapnia. Cortical spreading depression (CSD) also transiently reduces hypercapnic vasodilation. The authors sought to determine whether the CSD elicited by a controlled cortical impact (CCI) injury masks the true effect of TBI on hypercapnic vasodilation, and whether a nitric oxide (NO) donor can reverse the attenuation of hypercapnic vasodilation following CCI.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Methods.<\/jats:italic> Anesthetized rats underwent moderate CCI. Cerebral blood flow was monitored with laser Doppler flowmetry and the response to hypercapnia was determined for injured and sham-injured animals. The effect of the NO donor, S-nitroso-<jats:italic>N<\/jats:italic>-acetylpenicillamine (SNAP), on this response was also assessed.<\/jats:p>\n<jats:p content-type=\"fine-print\">At an uninjured cortical site ipsilateral to the CCI, a single wave of CSD was recorded and the CO<jats:sub>2<\/jats:sub> response at this location was significantly attenuated for up to 30 minutes (seven rats, p &lt; 0.05). At the injured cortex, hypercapnic vasodilation continued to be attenuated for 7 hours. The cerebral vasodilation to CO<jats:sub>2<\/jats:sub> was 37 \u00b1 5% in injured rats (six) compared with 84 \u00b1 10% in the sham-injured group (five rats, p &lt; 0.05). After 30 minutes of topical superfusion with SNAP, hypercapnic vasodilation was restored to 74 \u00b1 7% (nine rats, p &gt; 0.1 compared with that in the sham-injured group). In contrast, papaverine, an NO-independent vasodilator, failed to reverse the attenuation of the CO<jats:sub>2<\/jats:sub> response to CCI.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Conclusions.<\/jats:italic> The authors conclude that CSD elicited by CCI can mask the true effect of TBI on hypercapnic vasodilation for at least 30 minutes. Exogenous NO, but not papaverine, can reverse the attenuation of cerebrovascular reactivity to CO<jats:sub>2<\/jats:sub> caused by TBI. This result supports the hypothesis that NO production is reduced after TBI and that the NO donor has a potential beneficial role in the clinical management of head injury.<\/jats:p>","DOI":"10.3171\/jns.2002.97.4.0963","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T17:45:47Z","timestamp":1242236747000},"page":"963-969","source":"Crossref","is-referenced-by-count":22,"title":["Reversal of attenuation of cerebrovascular reactivity to hypercapnia by a nitric oxide donor after controlled cortical impact in a rat model of traumatic brain injury"],"prefix":"10.3171","volume":"97","author":[{"given":"Fangyi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane M.","family":"Sprague","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrokh","family":"Farrokhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew N.","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minnette G.","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis G.","family":"Vollmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1089\/neu.1998.15.627","article-title":"Effects of moderate, central fluid percussion traumatic brain injury on nitric oxide synthase activity in rats.","volume":"15","author":"Alagarsamy","year":"1998"},{"key":"b2","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"901","DOI":"10.3171\/jns.1996.85.5.0901","article-title":"Role of endothelin in pial artery vasoconstriction and altered responses to vasopressin after brain injury.","volume":"85","author":"Armstead","year":"1996"},{"key":"b3","series-title":"Anesth Analg","first-page":"687","article-title":"Regional cerebral blood flow after controlled cortical impact injury in rats.","volume":"80","author":"Bryan","year":"1995"},{"key":"b4","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1089\/neu.1997.14.35","article-title":"Extracellular release of serotonin following fluid-percussion brain injury in rats.","volume":"14","author":"Busto","year":"1997"},{"key":"b5","series-title":"Brain Inj","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1080\/02699050119009","article-title":"Cognitive deficits following blast injury-induced neurotrauma: possible involvement of nitric oxide.","volume":"15","author":"Cernak","year":"2001"},{"key":"b6","series-title":"Crit Care Med","doi-asserted-by":"publisher","first-page":"2512","DOI":"10.1097\/00003246-199911000-00031","article-title":"Cerebral hemodynamic effects of phenylephrine and L-arginine after cortical impact injury.","volume":"27","author":"Cherian","year":"1999"},{"key":"b7","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1089\/neu.1994.11.573","article-title":"Lateral cortical impact injury in rats: cerebrovascular effects of varying depth of cortical deformation and impact velocity.","volume":"11","author":"Cherian","year":"1994"},{"key":"b8","series-title":"Acta Anaesthesiol Scand","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1111\/j.1399-6576.1977.tb01232.x","article-title":"The effects of PaCO2 reduction on regional cerebral blood flow in the acute phase of brain injury.","volume":"21","author":"Cold","year":"1977"},{"key":"b9","series-title":"Am J Physiol","first-page":"H1315","article-title":"Neuronal NO promotes cerebral cortical hyperemia during cortical spreading depression in rabbits.","volume":"272","author":"Colonna","year":"1997"},{"key":"b10","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1089\/neu.1997.14.223","article-title":"L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion after fluid-percussion traumatic brain injury.","volume":"14","author":"DeWitt","year":"1997"},{"key":"b11","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1097\/00004647-199605000-00015","article-title":"Widespread hemodynamic depression and focal platelet accumulation after fluid percussion brain injury: a double-label autoradiographic study in rats.","volume":"16","author":"Dietrich","year":"1996"},{"key":"b12","series-title":"J Neurosci Methods","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/0165-0270(91)90104-8","article-title":"A controlled cortical impact model of traumatic brain injury in the rat.","volume":"39","author":"Dixon","year":"1991"},{"key":"b13","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"689","DOI":"10.3171\/jns.1978.48.5.0689","article-title":"Autoregulation and CO2 responses of cerebral blood flow in patients with acute severe head injury.","volume":"48","author":"Enevoldsen","year":"1978"},{"key":"b14","series-title":"Am J Physiol","first-page":"H23","article-title":"Arginine-nitric oxide pathway and cerebrovascular regulation in cortical spreading depression.","volume":"269","author":"Fabricius","year":"1995"},{"key":"b15","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/0006-8993(93)90701-N","article-title":"Transient hyperemia succeeds oligemia in the wake of cortical spreading depression.","volume":"602","author":"Fabricius","year":"1993"},{"key":"b16","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1097\/00004647-199708000-00005","article-title":"Assessment of cerebral blood flow and CO2 reactivity after controlled cortical impact by perfusion magnetic resonance imaging using arterial spin-labeling in rats.","volume":"17","author":"Forbes","year":"1997"},{"key":"b17","series-title":"Neurosurgery","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1093\/neurosurgery\/46.1.169","article-title":"Temporal profiles and cellular sources of three nitric oxide synthase isoforms in the brain after experimental contusion.","volume":"46","author":"Gahm","year":"2000"},{"key":"b18","series-title":"Acta Neurochir","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/BF01405899","article-title":"The relation between intracranial pressure, mean arterial pressure and cerebral blood flow in patients with severe head injury.","volume":"32","author":"Gobiet","year":"1975"},{"key":"b19","series-title":"Clin Exp Hypertens","doi-asserted-by":"publisher","first-page":"299","DOI":"10.3109\/10641969909068668","article-title":"The consequences of traumatic brain injury on cerebral blood flow and autoregulation: a review.","volume":"21","author":"Golding","year":"1999"},{"key":"b20","series-title":"Am J Physiol","first-page":"H1457","article-title":"Cerebrovascular reactivity to CO(2) and hypotension after mild cortical impact injury.","volume":"277","author":"Golding","year":"1999"},{"key":"b21","series-title":"Brain Res Brain Res Rev","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/S0165-0173(01)00081-9","article-title":"Spreading depression: a review of the clinical relevance.","volume":"38","author":"Gorji","year":"2001"},{"key":"b22","series-title":"Magn Reson Med","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1002\/(SICI)1522-2594(199910)42:4<673::AID-MRM8>3.0.CO;2-B","article-title":"Early perfusion after controlled cortical impact in rats: quantification by arterial spin-labeled MRI and the influence of spin-lattice relaxation time heterogeneity.","volume":"42","author":"Hendrich","year":"1999"},{"key":"b23","series-title":"Proc Nat Acad Sci USA","doi-asserted-by":"publisher","first-page":"3913","DOI":"10.1073\/pnas.89.9.3913","article-title":"Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia?","volume":"89","author":"Iadecola","year":"1992"},{"key":"b24","series-title":"Am J Physiol","first-page":"R1156","article-title":"Nitric oxide participates in the cerebrovasodilation elicited from cerebellar fastigial nucleus.","volume":"263","author":"Iadecola","year":"1992"},{"key":"b25","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/jcbfm.1990.112","article-title":"Continuous monitoring of cerebrocortical blood flow during stimulation of the cerebellar fastigial nucleus: a study by laser-Doppler flowmetry.","volume":"10","author":"Iadecola","year":"1990"},{"key":"b26","series-title":"Am J Physiol","first-page":"R990","article-title":"Permissive and obligatory roles of NO in cerebrovascular responses to hypercapnia and acetylcholine.","volume":"271","author":"Iadecola","year":"1996"},{"key":"b27","series-title":"Am J Physiol","first-page":"R228","article-title":"SIN-1 reverses attenuation of hypercapnic cerebrovasodilation by nitric oxide synthase inhibitors.","volume":"267","author":"Iadecola","year":"1994"},{"key":"b28","series-title":"J Trauma","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1097\/00005373-199310000-00015","article-title":"Nitric oxide production is inhibited in trauma patients.","volume":"35","author":"Jacob","year":"1993"},{"key":"b29","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1089\/neu.1995.12.1015","article-title":"Severe controlled cortical impact in rats: assessment of cerebral edema, blood flow, and contusion volume.","volume":"12","author":"Kochanek","year":"1995"},{"key":"b30","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"803","DOI":"10.3171\/jns.1986.64.5.0803","article-title":"Superoxide production in experimental brain injury.","volume":"64","author":"Kontos","year":"1986"},{"key":"b31","series-title":"Exp Neurol","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/0014-4886(92)90137-F","article-title":"Spreading depression induces prolonged reduction of cortical blood flow reactivity in the rat.","volume":"117","author":"Lacombe","year":"1992"},{"key":"b32","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1038\/jcbfm.1984.79","article-title":"Long-lasting reduction of cortical blood flow of the brain after spreading depression with preserved autoregulation and impaired CO2 response.","volume":"4","author":"Lauritzen","year":"1984"},{"key":"b33","series-title":"J Neurophysiol","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1152\/jn.1944.7.6.359","article-title":"Spreading depression of activity in the cerebral cortex.","volume":"7","author":"Leao","year":"1944"},{"key":"b34","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"500","DOI":"10.3171\/jns.1980.53.4.0500","article-title":"Autoregulation of cerebral blood flow after experimental fluid percussion injury of the brain.","volume":"53","author":"Lewelt","year":"1980"},{"key":"b35","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"332","DOI":"10.3171\/jns.1982.56.3.0332","article-title":"Effects of experimental fluid-percussion injury of the brain on cerebrovascular reactivity of hypoxia and to hypercapnia.","volume":"56","author":"Lewelt","year":"1982"},{"key":"b36","series-title":"Mol Chem Neuropathol","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/BF02815154","article-title":"Inhibition of nitric oxide synthase potentiates hypertension and increases mortality in traumatically brain-injured rats.","volume":"30","author":"Lu","year":"1997"},{"key":"b37","series-title":"Acta Neurochir Suppl","first-page":"63","article-title":"Brain viability and function analyzer: multiparametric real-time monitoring in neurosurgical patients.","volume":"75","author":"Mayevsky","year":"1999"},{"key":"b38","series-title":"Acta Neurochir Suppl","first-page":"78","article-title":"Real-time multiparametric monitoring of the injured human cerebral cortex\u2014a new approach.","volume":"71","author":"Mayevsky","year":"1998"},{"key":"b39","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1089\/neu.1996.13.209","article-title":"Reduction of the neurological deficit in mice with traumatic brain injury by nitric oxide synthase inhibitors.","volume":"13","author":"Mesenge","year":"1996"},{"key":"b40","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1089\/neu.1996.13.201","article-title":"Continuous measurement of changes in regional cerebral blood flow following cortical compression contusion trauma in the rat.","volume":"13","author":"Nilsson","year":"1996"},{"key":"b41","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1089\/neu.1999.16.865","article-title":"Traumatic injury to rat brain upregulates neuronal nitric oxide synthase expression and L-[3H] nitroarginine binding.","volume":"16","author":"Rao","year":"1999"},{"key":"b42","series-title":"Neurosci Lett","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0304-3940(98)00442-X","article-title":"Nitric oxide does not mediate cerebral blood flow changes during cortical spreading depression in the anaesthetised rat.","volume":"250","author":"Read","year":"1998"},{"key":"b43","series-title":"J Neurol Neurosurg Psychiatry","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1136\/jnnp.55.7.594","article-title":"Cerebral blood flow, arteriovenous oxygen difference, and outcome in head injured patients.","volume":"55","author":"Robertson","year":"1992"},{"key":"b44","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3171\/jns.1979.51.1.0018","article-title":"The effects of graded experimental trauma on cerebral blood flow and responsiveness to CO2.","volume":"51","author":"Saunders","year":"1979"},{"key":"b45","series-title":"Can J Physiol Pharmacol","doi-asserted-by":"publisher","first-page":"S248","DOI":"10.1139\/y92-268","article-title":"Mechanism of spreading depression: a review of recent findings and a hypothesis.","volume":"70","author":"Somjen","year":"1992"},{"key":"b46","series-title":"Brain Res","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/S0006-8993(00)02827-4","article-title":"Effects of brain oxygenation on metabolic, hemodynamic, ionic and electrical responses to spreading depression in the rat.","volume":"882","author":"Sonn","year":"2000"},{"key":"b47","series-title":"Neurosurg Rev","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1007\/BF01790682","article-title":"Hypermetabolic state following experimental head injury.","volume":"12","author":"Sunami","year":"1989"},{"key":"b48","series-title":"J Neurotrauma","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1089\/neu.1999.16.203","article-title":"Effects of L-NAME and 7-NI on NOS catalytic activity and behavioral outcome after traumatic brain injury in the rat.","volume":"16","author":"Wada","year":"1999"},{"key":"b49","series-title":"J Neurosurg","doi-asserted-by":"publisher","first-page":"807","DOI":"10.3171\/jns.1998.89.5.0807","article-title":"Role of nitric oxide in traumatic brain injury in the rat.","volume":"89","author":"Wada","year":"1998"},{"key":"b50","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/jcbfm.1991.117","article-title":"Alterations in regional cerebral blood flow following brain injury in the rat.","volume":"11","author":"Yamakami","year":"1991"},{"key":"b51","series-title":"Neuroscience","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1016\/0306-4522(95)00302-Y","article-title":"Role of nitric oxide and acetylcholine in neocortical hyperemia elicited by basal forebrain stimulation: evidence for an involvement of endothelial nitric oxide.","volume":"69","author":"Zhang","year":"1995"},{"key":"b52","series-title":"J Cereb Blood Flow Metab","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1038\/jcbfm.1994.125","article-title":"Cerebral blood flow changes during cortical spreading depression are not altered by inhibition of nitric oxide synthesis.","volume":"14","author":"Zhang","year":"1994"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/97\/4\/article-p963.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/97\/4\/article-p963.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/97\/4\/article-p963.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T01:09:48Z","timestamp":1679274588000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/97\/4\/article-p963.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,10]]},"references-count":52,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3171\/jns.2002.97.4.0963","relation":{},"ISSN":["0022-3085"],"issn-type":[{"value":"0022-3085","type":"print"}],"subject":[],"published":{"date-parts":[[2002,10]]}}}