Neuroprotective effects of gabapentin on spinal cord ischemia-reperfusion injury in rabbits

Kale, Aydemir; Börcek, Alp Özgün; Emmez, Hakan; Yıldırım, Zühal; Durdağ, Emre; Lortlar, Neşe; Kurt, Gökhan; Doğulu, Fikret; Kılıç, Nedret

doi:10.3171/2011.4.spine10583

Cited by 36 publications

(30 citation statements)

References 51 publications

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“…In each field, microglia and astrocyte infiltration was graded as follows: + = normal, ++ = slight infiltration, +++ = moderate infiltration, ++++ = severe infiltration. 15 …”

Section: Histological Evaluationmentioning

confidence: 99%

Effects of curcumin on acute spinal cord ischemia-reperfusion injury in rabbits

Kurt

Yıldırım²,

Cemil

et al. 2014

SPI

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Object. The object of this study was to conduct a prospective, randomized, laboratory investigation of the neuroprotective effects of curcumin functionally, biochemically, and histologically in an experimental acute spinal cord ischemia-reperfusion injury on rabbits.Methods. Eighteen rabbits were randomly assigned to 1 of 3 groups: the sham group, the ischemia-reperfusion group, or the curcumin group. Spinal cord ischemia was induced by applying an infrarenal aortic cross-clamp for 30 minutes. At 48 hours after ischemia, neurological function was evaluated with modified Tarlov criteria. Biochemical changes in the spinal cord and plasma were observed by measuring levels of malondialdehyde (MDA), advanced oxidation protein products (AOPP), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), nitrite/nitrate, and tumor necrosis factor-a (TNF-a). Histological changes were examined with H & E staining. Immunohistochemical staining with antibodies against caspase-3 was performed to evaluate cell apoptosis after ischemia.Results. In the curcumin group, neurological outcome scores were statistically significantly better compared with the ischemia-reperfusion group. In the ischemia-reperfusion group, MDA, AOPP, and nitrite/nitrate levels were significantly elevated in the spinal cord tissue and the plasma by the induction of ischemia-reperfusion. The curcumin treatment significantly prevented the ischemia-reperfusion-induced elevation of nitrite/nitrate and TNF-a. In addition, the spinal cord tissue and the plasma SOD, GSH, and CAT levels were found to be preserved in the curcumin group and not statistically different from those of the sham group. Histological evaluation of the tissues also demonstrated a decrease in axonal damage, neuronal degeneration, and glial cell infiltration after curcumin administration.Conclusions. Although further studies including different dose regimens and time intervals are required, curcumin could attenuate a spinal cord ischemia-reperfusion injury in rabbits via reducing oxidative products and proinflammatory cytokines, as well as increasing activities of antioxidant enzymes and preventing apoptotic cell death. (http://thejns.org/doi/abs/10.3171/2013 keY WorDs • antioxidant • curcumin • ischemia-reperfusion injury • neuroprotection • oxidative stress • spinal cord injuryAbbreviations used in this paper: AOPP = advanced oxidation protein products; CAT = catalase; GSH = glutathione; MDA = malondialdehyde; SOD = superoxide dismutase; TBARS = thiobarbituric acid reactive substances; TNF = tumor necrosis factor.

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“…In each field, microglia and astrocyte infiltration was graded as follows: + = normal, ++ = slight infiltration, +++ = moderate infiltration, ++++ = severe infiltration. 15 …”

Section: Histological Evaluationmentioning

confidence: 99%

Effects of curcumin on acute spinal cord ischemia-reperfusion injury in rabbits

Kurt

Yıldırım²,

Cemil

et al. 2014

SPI

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“…The intensity of degenerated neurons was calculated in each field. Glial cell infiltration was graded as +1, +2, +3 and +4 according to their intensity in each field (31).…”

Section: █ Materials and Methodsmentioning

confidence: 99%

Effects of atorvastatin on experimental spinal cord ischemia-reperfusion injury in rabbits

Kardeş

Çivi²,

Tufan³

et al. 2016

Turkish Neurosurgery

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ABSTRACT(ROS), and lipid peroxidation (43). Studies have demonstrated increased glutamate release, activation of glutamate receptors and accumulation of calcium result in increased glutamate (3,21).Statins are a group of drugs that competitively inhibit the 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the first enzyme of the HMG-CoA reductase pathway. This inhibition impedes production of mevalonate, the next molecule in the cascade producing cholesterol. This action ultimately █ INTRODUCTION S pinal cord injury (SCI) is a mechanical insult followed by a secondary cascade of biologic events promoting permanent tissue damage. Excitotoxicity, oxidative stress and inflammatory response are the mediators of secondary injury, which is -theoretically-preventable (5,16). In the central nervous system (CNS), ischemic traumatic injury, cell loss and neuronal dysfunction, is thought to be the result of glutamatemediated excitotoxicity, formation of reactive oxygen species AIm: Extent of secondary injury is the determinant of tissue destruction and functional worsening after primary spinal cord injury (SCI). Data have accumulated on alleviation of secondary injury in SCI from many studies on the subject. Besides its cholesterol lowering effects, statins are known to have anti-inflammatory and anti-oxidant effects which are the main targets of spinal cord research. This study aims to evaluate the effects of atorvastatin on experimental spinal cord ischemia-reperfusion injury. mATERIAl and mEThODS: Thirty adult male New Zealand rabbits were allocated into control, ischemia-reperfusion (I/R) and treatment groups. Treatment group received 5 mg/kg of atorvastatin via lavage for the preceding 14 days. Other groups received placebo during the same time period. After two weeks, animals in the I/R and treatment groups underwent abdominal temporary aorta occlusion for 30 minutes. Neurological condition of the animals was recorded during the 48 hours of observation. Afterwards, animals were sacrificed and levels of malondialdehyde, glutathione and nitric oxide in spinal cord tissue and plasma and the histopathological tissue changes were determined. RESUlTS:Animals in the treatment groups demonstrated significantly better results than the I/R group regarding biochemical markers. Neurological evaluation using the Tarlov scale demonstrated significantly better results at the 48 th hour in treatment group. Histopathological results were also better in the treatment groups. CONClUSION:Results of this study demonstrate the neuroprotective effects of atorvastatin. Atorvastatin has favorable effects on biochemical markers of oxidative stress in SCI. Further studies with larger cohorts and different time periods are also needed.

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“…Unlike TPM, for which neuroprotection in conditions linked to both epilepsy and ischemia was demonstrated [18][19][20][21], studies regarding GP neuroprotection are scarce and contradictory [15,17]. Together with pregabalin and vigabatrin, GP belongs to the GABA analog group of anticonvulsants and it is a well-tolerated drug in most patients, with a mild side-effect profile.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, binding of the compound to the voltage-gated Ca 2+ channel α2-δ1 auxiliary subunit with selective inhibitory e ect was demonstrated [9,10]. GP was not extensively tested as a neuroprotective agent, the few existing studies have produced contradictory results, suggesting both efficiency [11][12][13][14][15] or ine ciency [16,17] having being reported [8]. A bulk of coherent evidence supports the protective role of TPM in both epilepsy [18,19] and other models of neurodegeneration [6,20,21].…”

Section: Introductionmentioning

confidence: 99%

Gabapentin is neuroprotective through glutamate receptor-independent mechanisms in staurosporine-induced apoptosis of cultured rat cerebellar neurons

Popescu

Ţuineag

Stoica

2013

Translational Neuroscience

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The anticonvulsants that are currently available modulate the activity of neuronal receptors and ion channels, which are equally involved in apoptotic pathways. We investigated the hypothesis that gabapentin (GP), an anticonvulsant without effect on glutamate receptors acting as GABA analog, has neuroprotective properties. For comparison, we chose topiramate (TPM), which has been reported to be neuroprotective via AMPA receptors blockade. For this purpose, we used rat cerebellar granule neuron (CGN) cultures and we triggered apoptosis independent of glutamate receptors with staurosporine, a broad-spectrum protein kinase inhibitor. GP at therapeutic range concentration significantly increased cell viability in CGN cultures maintained in physiological KCl concentration and reversed apoptosis induced by staurosporine. Blockade of NMDA or AMPA receptors by MK801 or NBQX, respectively, did not alter GP neuroprotection, which was reversed instead by GABA. In contrast, protective effect of TPM on STS-treated CGN cultures was annihilated by NBQX, and not altered by MK801 or GABA. Treatments with neuroprotective concentrations of GP or TPM did not modify the expression of neuronal cell adhesion molecule or synaptophysin or the morphological aspect of neuronal endings. In summary, we report that GP is neuroprotective through glutamate-receptor independent mechanisms and without alteration of neuronal plasticity markers, which makes it a possible candidate for clinical neuroprotection trials.

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Neuroprotective effects of gabapentin on spinal cord ischemia-reperfusion injury in rabbits

Cited by 36 publications

References 51 publications

Effects of curcumin on acute spinal cord ischemia-reperfusion injury in rabbits

Effects of curcumin on acute spinal cord ischemia-reperfusion injury in rabbits

Effects of atorvastatin on experimental spinal cord ischemia-reperfusion injury in rabbits

Gabapentin is neuroprotective through glutamate receptor-independent mechanisms in staurosporine-induced apoptosis of cultured rat cerebellar neurons

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