Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion

Asci, Sanem; Demirci, Serpil; Aşçı, Halil; Doğuç, Duygu Kumbul; Onaran, İbrahim

doi:10.5152/balkanmedj.2015.15742

Cited by 30 publications

(18 citation statements)

References 39 publications

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“…On the other hand, pretreatment with Pregb and NIL in the hippocampus was found to reverse an elevated NO level to an almost normal control level indicating that these drugs have powerful suppressive oxidant and anti-oxidant defence effects. This action can be further explained on the molecular level by the drug action on NF-κB and NRf2 pathways [7,33]. It was found that Pregb attenuates the expression of p-NF-κB and restore the activity and diminution of phosphorylation of NOS.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of nilotinib on pentylenetetrazol-induced epilepsy in adult rat hippocampus: involvement of oxidative stress, autophagy, inflammation, and apoptosis

Attia¹,

Elmansy²,

Elsaed³

2019

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Introduction: Neuronal cell death and glial cell activation are the main pathological findings induced by seizures secondary to oxidative stress. Previous studies have explained neuronal cell death on the basis of cell necrosis and apoptosis. Recent studies have attributed the neuronal loss to autophagy. The proved antioxidant and antifibrotic effect of nilotinib favours its use in the management of epileptic seizures. Aim of the study was to analyse the neuroprotective and antiepileptic effect of nilotinib and explain its mechanism of action. Material and methods: Forty adult male rats were divided into four groups: control, pentylenetetrazol (PTZ) group (injected with PTZ 60 mg/kg, s.c.), pregabalin (Pregb)-PTZ group (pretreated with pregabalin daily 30 mg/kg; orally for 1 week) and nilotinib (NIL)-PTZ group (pretreated with nilotinib, 25 mg/kg daily for 1 week) prior to PTZ. Seizure latency was evaluated, the hippocampus tissue level of antioxidant enzymes was assessed. The histopathological changes in the hippocampus were studied using hematoxylin and eosin stain and immunohistochemical stain for brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), beclin-1, nuclear factor kappa-B (NF-κB) and Bcl-2-like protein 4 (BAX). Results: Nilotinib induced an increase in the latency of seizures, enhanced the antioxidant levels of the γ-aminobutyric acid and nuclear factor (erythroid-derived 2)-like 2 activities together with the improvement of the hippocampal histology. A reduction was reported for BDNF, GFAP, beclin-1, NF-κB and BAX expression in nerve cells. Conclusions: Nilotinib may have promising neuroprotective and antiepileptic effects against pentylenetetrazolinduced seizures through promoting the antioxidant, antifibrotic, anti-inflammatory, antiapoptotic pathways and inhibiting autophagy.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of nilotinib on pentylenetetrazol-induced epilepsy in adult rat hippocampus: involvement of oxidative stress, autophagy, inflammation, and apoptosis

Attia¹,

Elmansy²,

Elsaed³

2019

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“…In another study, PGB showed antianxiety property by attenuation of left amygdala activation during fearful face‐matching and activation of left anterior insula during angry face‐matching, using emotional face‐matching task (Aupperle et al., 2012). The neuroprotection effect of PGB was recently evaluated in reperfusion after cerebral ischemia in rat brain injury (Asci, Demirci, Asci, Doguc, & Onaran, 2016) and also after traumatic brain injury, improving neurological function (Shamsi Meymandi et al., 2018). PGB reduced neuroinflammation, apoptosis, oxidative stress, and fibrosis in the optic nerve of diabetic rats (Ali, Zaitone, Dessouki, & Ali, 2019).…”

Section: Introductionmentioning

confidence: 99%

Prenatal pregabalin is associated with sex‐dependent alterations in some behavioral parameters in valproic acid‐induced autism in rat offspring

Meymandi

Sepehri

Moslemizadeh

et al. 2020

Intl J of Devlp Neuroscience

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This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)-induced autism-like symptoms. Pregnant rats received VPA (600 mg/kg/i.p.) once at 12.5 gestational days for autism-like symptom induction in offspring. After the delivery single male and single female offspring from each mother were randomly selected for behavioral test (anxiety, pain response, pleasure, and motor function) at 60th day adulthood (n = 7). Offspring received prenatal PGB (15 & 30 mg/kg/i.p.) during gestational days 9.5 to 15.5 either alone or in combination with VPA (PGB15, PGB30, PGB15 + VPA, and PGB30 + VPA). Control offspring received normal saline during the same period. The result showed that prenatal VPA exposure was associated with autism-like behaviors in rat offspring. PGB treatment during the gestational period revealed significant reduction in sucrose preference test and anxiety in elevated plus maze and open field test in offspring. Also, PGB treatments exhibited a dose-dependent increase in pain threshold in prenatally VPA exposed rats in tail-flick and hot plate test. Also, there was a sex-related significant impairment in motor function in beam balance and open field test, and male rats were affected more than females. However, no significant sex differences in sucrose preference and pain sensitivity were observed in prenatal PGB-treated rat offspring. In conclusion, prenatal exposure to VPA increased the risk of autism-like behaviors in the offspring rats, and PGB treatment during the gestational period was associated with some beneficial effects, including anxiety reduction and motor impairment in autism-like symptoms in rat offspring. K E Y W O R D S anhedonia, anxiety, autism, pain, pregabalin, valproic acid | 501 SHAMSI MEYMANDI Et Al. 1 | INTRODUCTION Autism spectrum disorder (ASD) is a complicated, behaviorally defined disorder, including communication and social interaction deficits and restricted, repetitive and stereotyped behaviors (Bolte et al., 2019). Prevalence estimates and diagnosis rates of ASD have risen substantially in the last two decades reaching 1.5% in developed countries (Lyall et al., 2017). According to the World Health Organization (WHO) report in 2018, 1 in 160 children had ASD. In most of cases, ASD is associated with epilepsy, since different studies showed that 22% to 38% of children with autism also suffer from comorbid epilepsy (

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“…Our main results were as follows: 1) the CAT level decreased in Group C, whereas it remained the same in Group P; 2) the TOS decreased in Group P, whereas it increased in Group C; and 3) in Group P, the TAS value in the reperfusion period was higher than that in the ischemia period. Although pregabalin is a GABA analogue, it is a potent new-generation antiepileptic agent; it exerts an effect by binding to the α2δ subunit of voltage-gated calcium channels, which causes a reduction in the Ca ++ influx, and by inhibiting the release of glutamate and noradrenaline from presynaptic terminals [4,8].…”

Section: Discussionmentioning

confidence: 99%

“…Owing to these products, the injury not only causes local tissue damage but also distant organ damage [1]. CAT is one of the most important antioxidant enzymes against ROS [8]. In numerous studies, IMA levels increased in cases of acute ischemia such as that of the skeletal muscles as well as cerebral, myocardial, and pulmonary infarction/ischemia [25].…”

Section: Discussionmentioning

confidence: 99%

“…Pregabalin is a gamma-aminobutyric acid (GABA) analogue that does not interact with GABA receptors. It reduces Ca ++ influx by binding to the α2δ subunit of voltage-gated calcium channels and consequently inhibits the release of neurotransmitters such as glutamate and noradrenaline [8]. However, the mechanism of the action of pregabalin is not yet completely understood, and it is currently indicated for the treatment of diabetic neuropathy, fibromyalgia, and anxiety.…”

Section: Introductionmentioning

confidence: 99%

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The effect of pregabalin on the tourniquet induced ischemia-reperfusion injury. A Prospective Randomized Study

Karaca¹,

Pınar²,

Ozgur³

et al. 2019

Turk J Med Sci

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The aim of this study was to investigate the efficacy of pregabalin on ischemia-reperfusion injuries. Materials and methods: Fifty-four patients were randomly assigned into 2 groups. A 150-mg tablet of pregabalin was given the night before and then 1 h before the operation for patients in Group P (pregabalin group, n = 27). A placebo was given to patients in Group C (control group, n = 27) at the same times. After combined spinal-epidural anesthesia was performed, venous blood samples were taken before tourniquet inflation (t 1), just before tourniquet deflation (t 2), and 20 min after tourniquet deflation (t 3) for the analysis of total antioxidant status (TAS), total oxidant status (TOS), catalase (CAT), and ischemia-modified albumin (IMA). Results: There was no significant difference in TAS levels between the groups for the t 3 period. However, the TAS in Group P was significantly higher in the t 3 period than the t 2 period (mean ± SD, 0.46 ± 0.1 vs. 0.38 ± 0.2 mmol of Trolox equivalent/L, respectively; P < 0.05). The CAT level in the t 3 period was significantly higher in Group P than Group C (mean ± SD, 53.04 ± 32.1 vs. 35.46 ± 17.2 µmol/ formaldehyde, respectively; P < 0.05). In the t 3 period, the TOS was significantly lower in Group P than Group C (mean ± SD, 11.97 ± 5 vs. 18.29 ± 9.9 pg/mL, respectively; P < 0.05). The TOS in Group P was significantly lower in the t 3 period than the t 2 period (mean ± SD, 11.97 ± 5 vs. 18.98 ± 10.7 pg/mL, respectively; P < 0.0001). Conclusion: Pregabalin has no marked antioxidant activity, but it contributes to the antioxidant defense system of an organism.

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Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion

Abstract: Pregabalin may protect the damage of oxidative stress after ischemia + reperfusion. This result would illuminate clinical studies in the future.

Cited by 30 publications

References 39 publications

Neuroprotective effect of nilotinib on pentylenetetrazol-induced epilepsy in adult rat hippocampus: involvement of oxidative stress, autophagy, inflammation, and apoptosis

Neuroprotective effect of nilotinib on pentylenetetrazol-induced epilepsy in adult rat hippocampus: involvement of oxidative stress, autophagy, inflammation, and apoptosis

Prenatal pregabalin is associated with sex‐dependent alterations in some behavioral parameters in valproic acid‐induced autism in rat offspring

The effect of pregabalin on the tourniquet induced ischemia-reperfusion injury. A Prospective Randomized Study

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