Photobiomodulation combination therapy as a new insight in neurological disorders: a comprehensive systematic review.

Preclinical and clinical studies have indicated that combining photobiomodulation (PBM) therapy with other therapeutic approaches may influence the treatment process in a variety of disorders. The purpose of this systematic review was to determine whether PBM-combined therapy provides additional benefits over monotherapies in neurologic and neuropsychiatric disorders. In addition, the review describes the most commonly used methods and PBM parameters in these conjunctional approaches.To accomplish this, a systematic search was conducted in Google Scholar, PubMed, and Scopus databases through January 2024. 95 potentially eligible articles on PBM-combined treatment strategies for neurological and neuropsychological disorders were identified, including 29 preclinical studies and 66 clinical trials.According to the findings, seven major categories of studies were identified based on disease type: neuropsychiatric diseases, neurodegenerative diseases, ischemia, nerve injury, pain, paresis, and neuropathy. These studies looked at the effects of laser therapy in combination with other therapies like pharmacotherapies, physical therapies, exercises, stem cells, and experimental materials on neurological disorders in both animal models and humans. The findings suggested that most combination therapies could produce synergistic effects, leading to better outcomes for treating neurologic and psychiatric disorders and relieving symptoms.These findings indicate that the combination of PBM may be a useful adjunct to conventional and experimental treatments for a variety of neurological and psychological disorders.

Maternal vitamin D supplementation and treadmill exercise attenuated vitamin D deficiency-induced anxiety-and depressive-like behaviors in adult male offspring rats.

BACKGROUND: Vitamin D is a vital neuroactive steroid for brain development and function. Vitamin D deficiency is a worldwide health problem, particularly in children and women. Gestational or developmental vitamin D deficiency is associated with an increased risk of neurodevelopmental and neuropsychiatric disorders. This study examined the effect of maternal vitamin D dietary manipulations and treadmill exercise on anxiety-and depressive-related behaviors, pro-inflammatory cytokines, and prefrontal cortex (PFC) protein levels of brain-derived neurotrophic factor (BDNF) and vitamin D receptor (VDR) in adult male offspring born to vitamin D-deficient diet (VDD)-fed dams. METHODS AND RESULTS: Female rats were provided standard diet (SD) or VDD for six weeks and then were treated with SD (started a week before mating throughout gestation and lactation) and treadmill exercise (a week before mating until gestational day 20). Male offspring were separated on postnatal day (PND) 21 and fed SD chow until PND90. Our results demonstrated that maternal vitamin D deficiency increased anxiety and depression-related behaviors, increased levels of TNF-α and IL-1ß in serum, and decreased prefrontal protein expressions of BDNF and VDR in adult male offspring. However, maternal vitamin D supplementation and treadmill exercise reversed these changes alone or in combination. CONCLUSION: It seems that developmental vitamin D deficiency disrupts brain development and has a long-lasting effect on VDR and BDNF signaling in the rat brain resulting in neuropsychiatric disorders in offspring. Therefore, vitamin D supplementation and physical exercise are reasonable strategies to prevent these neurobehavioral impairments.

Synergistic effects of combined therapy with transcranial photobiomodulation and enriched environment on depressive- and anxiety-like behaviors in a mice model of noise stress.

The development of anxiety and depression due to chronic exposure to noise stress has remained as an unsolved health problem so far. Despite the studies suggesting the neuroenhancement effects of transcranial photobiomodulation (tPBM) and housing in an enriched environment (EE), the combined effects of these treatments have not been elucidated yet. Also, there is no available data on the relationship between the application of tPBM and hippocampal brain-derived neurotrophic factor (BDNF) expression in animal models of stress. The present study aims to investigate the application of the tPBM and EE (alone or in combination) on depressive- and anxiety-like behaviors in a mice model of noise stress. Mice were divided into five groups: control, noise, noise + EE, noise + tPBM, and noise + EE + tPBM. Except for the control group, other groups were subjected to 110 dB SPL white noise for 4 h/day for 14 consecutive days and received their respective treatments. Forced Swimming Test (FST) was used to evaluate depressive-like behaviors. Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to evaluate anxiety-like behaviors. BDNF, tyrosine receptor kinase B (TrkB), and cAMP response element-binding (CREB) protein levels in the hippocampus were determined by the Western blot method, and also serum corticosterone levels were assessed using an ELISA kit. Exposure to noise stress significantly elevated serum corticosterone level; downregulated hippocampal BDNF, TrkB, and CREB protein expressions; and resulted in depressive- and anxiety-like behaviors. While, the application of tPBM (810 nm wavelength, 8 J/cm2 fluence, 10 Hz pulsed wave mode), housing in EE, and their combination lowered corticosterone levels, upregulated the BDNF/TrkB/CREB signaling pathway in the hippocampus, and improved behavioral outcomes in noise stress subjected mice. Our finding revealed the improving effects of tPBM and EE on depressive and anxiety-like behaviors induced by noise stress, possibly by augmenting the BDNF/TrkB/CREB signaling pathway.

The role of hippocampal GABAA receptors on anxiolytic effects of Echium amoenum extract in a mice model of restraint stress.

Echium amoenum (EA), a popular medicinal plant in Persian medicine, has anxiolytic, antioxidant, sedative, and anti-inflammatory effects. This study examined whether GABA-ergic signaling is involved in the anxiolytic effects of EA in mice. Sixty BALB/c mice (25-30 g) were divided into six groups (n = 10) as follows: the (I) control group received 10 ml/kg normal saline (NS). In the stress groups, the animals underwent 14 consecutive days of restraint stress (RS), and received following treatments simultaneously; (II) RS + NS; (III) RS + Diaz (Diazepam); (IV) RS + EA; (V) RS + Flu (Flumazenil) + EA; (VI) RS + Flu + Diaz. Behavioral tests including the open field test (OFT) and elevated plus maze (EPM) were performed to evaluate anxiety-like behaviors and the effects of the regimens. The plasma level of corticosterone and the hippocampal protein expressions of IL-1ß, TNF-α, CREB, and BDNF, as well as p-GABAA/GABAA ratio, were also assessed. The findings revealed that chronic administration of EA alone produced anxiolytic effects in both behavioral tests, while diazepam alone or in combination with Flu failed to decrease the anxiety-like behaviors. Furthermore, the p-GABAA/GABAA and p-CREB/CREB ratios, and protein levels of BDNF were significantly increased in the EA-received group. On the other hand, plasma corticosterone levels and the hippocampal IL-1ß and TNF-α levels were significantly decreased by EA. However, pre-treatment with GABAA receptors (GABAA Rs) antagonist, Flu, reversed the anxiolytic and molecular effects of EA in the RS-subjected animals. Our findings confirmed that alternation of GABAAR is involved in the effects of EA against RS-induced anxiety-like behaviors, HPA axis activation, and neuroinflammation.

Melissa officinalis L. hydro-alcoholic extract inhibits anxiety and depression through prevention of central oxidative stress and apoptosis.

NEW FINDINGS: What is the central question of this study? How does an extract of Melissa officinalis L. ameliorate anxiety- and depressive-like behaviour of mice? What is the main finding and its importance? An extract of Melissa officinalis L. possessed anxiolytic and anti-depressant effects, which could mainly be mediated through its antioxidant and anti-apoptotic properties. ABSTRACT: This study evaluated the effects of a hydro-alcoholic extract of Melissa officinalis (HAEMO) on anxiety- and depressive-like behaviours, oxidative stress and apoptosis markers in restraint stress-exposed mice. In order to induce a depression-like model, mice were subjected to restraint stress (3 h day-1 for 14 days) and received normal saline or HAEMO (50, 75 and 150 mg kg-1  day-1 ) for 14 days. The administered doses of HAEMO were designated based on the concentration of one of the main phenolic compounds present in the extract, rosmarinic acid (2.55 mg kg-1 at lowest dose); other phytochemical analyses including assays for antioxidant activity, total phenols and flavonoids were also carried out. The behavioural changes in an open field task, elevated plus maze, tail suspension and forced swimming tests were evaluated. Also, malondialdehyde (MDA) levels and enzyme activities of superoxide dismutase and glutathione peroxidase, and total antioxidant capacity were assessed in the prefrontal cortex and hippocampus. Moreover, levels of Bcl-2, Bax and caspase 3 in the brain as well as serum concentration of corticosterone were evaluated. HAEMO (75 and 150 mg kg-1 ) significantly reversed anxiety- and depressive-like behaviours. Also, HAEMO reduced MDA levels, enhanced enzymatic antioxidant activities and restored serum levels of corticosterone. An immunoblotting analysis also demonstrated that HAEMO decreased levels of pro-apoptotic markers and increased anti-apoptotic protein levels in the prefrontal cortex and hippocampus of restraint stress-exposed mice. Our findings suggested that HAEMO reduced inflammation and had anxiolytic and antidepressant effects in mice.

Therapeutic potential of intranasal photobiomodulation therapy for neurological and neuropsychiatric disorders: a narrative review.

The application of photobiomodulation therapy (PBMT) for neuronal stimulation is studied in different animal models and in humans, and has shown to improve cerebral metabolic activity and blood flow, and provide neuroprotection via anti-inflammatory and antioxidant pathways. Recently, intranasal PBMT (i-PBMT) has become an attractive and potential method for the treatment of brain conditions. Herein, we provide a summary of different intranasal light delivery approaches including a nostril-based portable method and implanted deep-nasal methods for the effective systemic or direct irradiation of the brain. Nostril-based i-PBMT devices are available, using either lasers or light emitting diodes (LEDs), and can be applied either alone or in combination to transcranial devices (the latter applied directly to the scalp) to treat a wide range of brain conditions such as mild cognitive impairment, Alzheimer's disease, Parkinson's disease, cerebrovascular diseases, depression and anxiety as well as insomnia. Evidence shows that nostril-based i-PBMT improves blood rheology and cerebral blood flow, so that, without needing to puncture blood vessels, i-PBMT may have equivalent results to a peripheral intravenous laser irradiation procedure. Up to now, no studies were conducted to implant PBMT light sources deep within the nose in a clinical setting, but simulation studies suggest that deep-nasal PBMT via cribriform plate and sphenoid sinus might be an effective method to deliver light to the ventromedial part of the prefrontal and orbitofrontal cortex. Home-based i-PBMT, using inexpensive LED applicators, has potential as a novel approach for neurorehabilitation; comparative studies also testing sham, and transcranial PBMT are warranted.

Garlic (Allium sativum) improves anxiety- and depressive-related behaviors and brain oxidative stress in diabetic rats.

This study investigated the effects of garlic on anxiety- and depression-related behaviors and brain oxidative markers in streptozotocin (STZ)-induced diabetes in rats. Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8/group): control, diabetic + saline, diabetic + garlic, diabetic + imipramine, and diabetic + diazepam groups. Animals received garlic homogenate (0.1, 0.25, and 0.5 g/kg) for 10 days. At the end of the treatments, anxiety- and depressive-related behaviors were evaluated by elevated plus maze (EPM) and forced swimming test (FST), respectively. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and malondialdehyde (MDA) levels were measured in the brain. Diabetic + garlic (0.5 g/kg) group showed lower anxiety- and- depressive-like behaviors as compared to the diabetic rats. Furthermore, garlic treatment (0.5 g/kg) attenuated MDA levels and enhanced SOD and GPx activities in the brain. Our findings indicate that garlic alleviates anxiety- and depression-related behaviors in the diabetic rats possibly by attenuation of brain oxidative stress.

Penetration Profiles of Visible and Near-Infrared Lasers and Light-Emitting Diode Light Through the Head Tissues in Animal and Human Species: A Review of Literature.

Background and objective: Photobiomodulation (PBM) therapy is a promising and noninvasive approach to stimulate neuronal function and improve brain repair. The optimization of PBM parameters is important to maximize effectiveness and tolerability. Several studies have reported on the penetration of visible-to-near-infrared (NIR) light through various animal and human tissues. Scientific findings on the penetration of PBM light vary, likely due to use of different irradiation parameters and to different characteristics of the subject such as species, age, and gender. Materials and methods: In this article, we review published data on PBM penetration through the tissues of the head in both animal and human species. The patterns of visible-to-NIR light penetration are summarized based on the following study specifications: wavelength, coherence, operation mode, beam type and size, irradiation site, species, age, and gender. Results: The average penetration of transcranial red/NIR (630-810 nm) light ranged 60-70% in C57BL/6 mouse (skull), 1-10% in BALB/c mouse (skull), 10-40% in Sprague-Dawley rats (scalp plus skull), 20% in Oryctolagus cuniculus rabbit (skull), 0.11% in pig (scalp plus skull), and 0.2-10% in humans (scalp plus skull). The observed variation in the reported values is due to the difference in factors (e.g., wavelengths, light coherence, tissue thickness, and anatomic irradiation site) used by researchers. It seems that these data challenge the applicability of the animal model data on transcranial PBM to humans. Nevertheless, two animal models seem particularly promising, as they approximate penetration in humans: (I) Penetration of 808 nm laser through the scalp plus skull was 0.11% in the pig head; (II) Penetration of 810 nm laser through intact skull was 1.75% in BALB/c mouse. Conclusions: In conclusion, it is worthwhile mentioning that since the effectiveness of brain PBM is closely dependent on the amount of light energy reaching the target neurons, further quantitative estimation of light penetration depth should be performed to validate the current findings.

Rosa canina L. methanolic extract prevents heat stress-induced memory dysfunction in rats.

NEW FINDINGS: What is the central question of this study? Heat stress has harmful effects on the brain structure and synaptic density via induction of oxidative stress and neuroinflammation, which result in neuronal damage in the hippocampus and thereby cognitive impairments. In this study, we investigate the effect of Rosa canina treatment on cognitive function in heat stress-exposed rats and its underlying mechanisms. What is the main finding and its importance? We show that R. canina improves cognitive deficits induced by heat stress by attenuation of oxidative stress and neuroinflammation and by upregulation of synaptic proteins in the hippocampus. ABSTRACT: The aim of the study was to evaluate the effects of aqueous methanolic extract of Rosa canina (RC) dried fruits on oxidative stress, inflammation, synaptic degeneration and memory dysfunction induced by heat stress (HS) in rats. Sixty adult male Wistar rats were randomly divided into five groups as follows: the control group received normal saline (NS); the HS group was exposed to heat stress (43°C) for 15 min once a day for 2 weeks; and HS+R groups were exposed to heat stress and received one of three doses (250, 500 or 1000 mg kg-1 ) of RC methanolic extract for 2 weeks. A passive avoidance test and a Y-maze test were performed to assess learning and memory. The levels of reactive oxygen species were assessed. The serum cortisol concentration and hippocampal total antioxidant capacity, superoxide dismutase and glutathione peroxidase were also detected using spectrophotometry. The protein expressions of c-Fos, heat-shock protein-70, tumour necrosis factor-α, growth-associated protein 43, post-synaptic density-95 and synaptophysin were evaluated in the hippocampal tissue. The results showed that RC significantly improved cognitive dysfunction induced by HS, which was accompanied by downregulation of tumour necrosis factor-α and upregulation of growth-associated protein 43 and synaptophysin proteins in the hippocampus of HS-exposed rats. Furthermore, RC significantly attenuated serum cortisol concentrations and upregulated heat shock protein-70 and c-Fos in the hippocampus. In addition, the administration of RC attenuated reactive oxygen species levels and enhanced antioxidant defense in the hippocampus. These findings indicate that RC attenuated the deleterious effect of HS on cognition through its antioxidant properties and by enhancing synaptic function and plasticity.

A Close Look at Echium amoenum Processing, Neuroactive Components, and Effects on Neuropsychiatric Disorders.

Pharmacological researches in the area of herbal medicine have considerably increased over the last two centuries. Echium amoenum (known as Gol-e-Gavzaban in Persian) is a medicinal plant that has been widely used in Iranian folk medicine. In this review, databases including PubMed, Scopus, and Google Scholar were searched up. Data collecting was completed by January 2019 and available scientific reports regarding the processing methods, main chemical constituents, and effects of E. amoenum on different neuropsychiatric disorders are summarized. Thirteen five studies met the inclusion criteria. According to results, the important phytochemicals of the plant was phenolic compounds, fatty acids, rosmarinic acid, anthocyanidins, and flavonoids. Also, experimental and clinical studies demonstrated the effectiveness of E. amoenum in the treatment of several neuropsychiatric disorders such as anxiety, depression, ischemic stroke, seizure, Alzheimer's disease, and pain. Many of these effects are, at least in part, due to its rosmarinic acid or polyphenolic compounds such as flavonoids and natural pigments such as anthocyanins. Also, fatty acids such as gamma-linolenic acid play critical role in neuroactive properties of this herb. Among these effects, only the antidepressant and anxiolytic properties of the plant extract have been examined both experimentally and clinically. There was some controversy over its toxicity effects. It seems that E. amoenum protects neurons via attenuation of oxidative stress and inflammation as well as blocking of apoptosis in the nervous system. However, more studies are necessary for assessing exact mechanisms of action in neuropsychiatric disorders, finding of bioactive ingredients, and processing methods of this plant.

Identification and applications of neuroactive silk proteins: a narrative review.

In traditional medicine, natural silk is regarded as a cognitive enhancer and a cure for ameliorating the symptoms of heart disease, atherosclerosis, and metabolic disorders. In this review, general characteristics of both silk proteins, fibroin and sericin, extracted from silkworm Bombyx mori and their potential use in the neuronal disorders was discussed. Evidence shows that silk proteins exhibit neuroprotective effects in models of neurotoxicity. The antioxidant, neuroprotective, and acetylcholinesterase inhibitory mechanisms of silk proteins could prove promising in the treatment of neurodegenerative diseases. Owing to their excellent neurocompatibility and physicochemical properties, silk proteins have been used as scaffolds and drug delivery materials in the neuronal tissue engineering. These data support the potential of silk proteins as an effective complementary agent for central and peripheral neurological disorders.

Near-infrared photobiomodulation combined with coenzyme Q10 for depression in a mouse model of restraint stress: reduction in oxidative stress, neuroinflammation, and apoptosis.

This study was aimed to evaluate the effects of near-infrared (NIR) photobiomodulation (PBM) combined with coenzyme Q10 (CoQ10) on depressive-like behavior, cerebral oxidative stress, inflammation, and apoptosis markers in mice. To induce a depressive-like model, mice were subjected to sub-chronic restraint stress for 5 consecutive days. NIR PBM (810 nm laser, 33.3 J/cm2) and/or CoQ10 (500 mg/kg/day, gavage) were administered for five days concomitantly with immobilization. Behavior was evaluated by the forced swim test (FST), tail suspension test (TST), and open field test (OFT). Mitochondrial membrane potential as well as oxidative stress, neuroinflammatory, and markers of apoptosis were evaluated in the prefrontal cortex (PFC) and hippocampus (HIP). The serum levels of pro-inflammatory cytokines, cortisol, and corticosterone were also measured. PBM or CoQ10, or the combination, ameliorated depressive-like behaviors induced by restraint stress as indicated by decreased immobility time in both the FST and TST. PBM and/or CoQ10 treatments decreased lipid peroxidation and enhanced total antioxidant capacity (TAC), GSH levels, GPx and SOD activities in both brain areas. The neuroinflammatory response in the HIP and PFC was suppressed, as indicated by decreased NF-kB, p38, and JNK levels in PBM and/or CoQ10 groups. Intrinsic apoptosis biomarkers, BAX, Bcl-2, cytochrome c release, and caspase-3 and -9, were also significantly down-regulated by both treatments. Furthermore, both treatments decreased the elevated serum levels of cortisol, corticosterone, TNF-α, and IL-6 induced by restraint stress. Transcranial NIR PBM and CoQ10 therapies may be effective antidepressant strategies for the prevention of psychopathological and behavioral symptoms induced by stress.

Effects of troxerutin on anxiety- and depressive-like behaviors induced by chronic mild stress in adult male rats.

OBJECTIVES: Chronic stress has been linked to the pathophysiology of mood disorders including anxiety and depression. In this study, we aimed to investigate the effect of troxerutin (TRX), as a flavonol, on stress-induced anxiety and depression. MATERIALS AND METHODS: 56 animals were randomly divided into seven groups (n=8 per group) as follows: control, saline, TRX 50, TRX 150, TRX 300, Diazepam, and Imipramine. Chronic mild stress (CMS) was induced by restraining animals in Plexiglas cylinders for 1 hr each day for 25 consecutive days. Different doses (50, 150, and 300 mg/kg, oral gavage) of troxerutin was gavaged for 14 consecutive days. At the end of treatments, anxiety- and depressive-like behaviors were tested using elevated plus-maze (EPM), open field test (OFT), and forced swimming test (FST). RESULTS: CMS significantly increased immobility (P<0.05) and decreased swimming (P<0.01) time in FST. However, different doses of troxerutin significantly decreased immobility (P<0.01) and increased swimming (P<0.001) time. CMS also significantly (P<0.01) decreased the percentage of open arm entrance (%OAE), whereas troxerutin significantly increased both %OAE and percentage of open arm time (%OAT) in the EPM. Moreover, CMS significantly decreased time spent in the center (P<0.001) and the number of center entrances (P<0.01) in the OFT. However, troxerutin significantly increased time spent in the center and number of the entrances crossing. Furthermore, CMS significantly increased serum cortisol levels and troxerutin decreased it. CONCLUSION: Troxerutin demonstrated anxiolytic- and antidepressant-like activities in rodents, which supports the use of herbal medicine in the mood disorders.

Transcranial near-infrared photobiomodulation attenuates memory impairment and hippocampal oxidative stress in sleep-deprived mice.

Sleep deprivation (SD) causes oxidative stress in the hippocampus and subsequent memory impairment. In this study, the effect of near-infrared (NIR) photobiomodulation (PBM) on learning and memory impairment induced by acute SD was investigated. The mice were subjected to an acute SD protocol for 72 h. Simultaneously, NIR PBM using a laser at 810 nm was delivered (once a day for 3 days) transcranially to the head to affect the entire brain of mice. The Barnes maze and the What-Where-Which task were used to assess spatial and episodic-like memories. The hippocampal levels of antioxidant enzymes and oxidative stress biomarkers were evaluated. The results showed that NIR PBM prevented cognitive impairment induced by SD. Moreover, NIR PBM therapy enhanced the antioxidant status and increased mitochondrial activity in the hippocampus of SD mice. Our findings revealed that hippocampus-related mitochondrial damage and extensive oxidative stress contribute to the occurrence of memory impairment. In contrast, NIR PBM reduced hippocampal oxidative damage, supporting the ability of 810 nm laser light to improve the antioxidant defense system and maintain mitochondrial survival. This confirms that non-invasive transcranial NIR PBM therapy ameliorates hippocampal dysfunction, which is reflected in enhanced memory function.

Enduring amnesia induced by ICV scopolamine is reversed by sesame oil in male rats.

PURPOSE: To evaluated the long-term effect of scopolamine and sesame oil on spatial memory. METHODS: Memory impairment induced by Intracerebroventricular (ICV) injection of scopolamine hydrochloride (10 µg/ rat). Animals were gavaged for 4 weeks with saline, sesame oil (0.5, 1, or 2 mL/kg/day), or 3 weeks with memantine (30 mg/kg/day) in advance to induction of amnesia. Morris water maze (MWM) test was conducted 6 days after microinjection of scopolamine. Then, blood and brain samples were collected and evaluated for the malondialdehyde (MDA) levels, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, and total antioxidant status (TAS) and ferric reducing ability of plasma (FRAP). RESULTS: Scopolamine significantly decreased traveled distance and time spent in target quadrant in probe test. Pretreatment of rats with sesame oil (0.5 mg/kg) mitigated scopolamine-induced behavioral alterations. Measurement of MDA, SOD, and GPX in brain tissue, and FRAP and TAS in blood showed little changes in animals which had received scopolamine or sesame oil. CONCLUSIONS: Intracerebroventricular injection of scopolamine has a residual effect on memory after six days. Sesame oil has an improving effect on spatial memory; however this effect is possibly mediated by mechanisms other than antioxidant effect of sesame oil.

Enduring amnesia induced by ICV scopolamine is reversed by sesame oil in male rats

ABSTRACT PURPOSE: To evaluated the long-term effect of scopolamine and sesame oil on spatial memory. METHODS: Memory impairment induced by Intracerebroventricular (ICV) injection of scopolamine hydrochloride (10 μg/ rat). Animals were gavaged for 4 weeks with saline, sesame oil (0.5, 1, or 2 mL/kg/day), or 3 weeks with memantine (30 mg/kg/day) in advance to induction of amnesia. Morris water maze (MWM) test was conducted 6 days after microinjection of scopolamine. Then, blood and brain samples were collected and evaluated for the malondialdehyde (MDA) levels, superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, and total antioxidant status (TAS) and ferric reducing ability of plasma (FRAP). RESULTS: Scopolamine significantly decreased traveled distance and time spent in target quadrant in probe test. Pretreatment of rats with sesame oil (0.5 mg/kg) mitigated scopolamine-induced behavioral alterations. Measurement of MDA, SOD, and GPX in brain tissue, and FRAP and TAS in blood showed little changes in animals which had received scopolamine or sesame oil. CONCLUSIONS: Intracerebroventricular injection of scopolamine has a residual effect on memory after six days. Sesame oil has an improving effect on spatial memory; however this effect is possibly mediated by mechanisms other than antioxidant effect of sesame oil.