Neuroinflammation and microglial expression in brains of social-isolation rearing model of schizophrenia.

Schizophrenia is a psychiatric disorder with a global prevalence of approximately 0.45%. It is considered a mental illness, with negative symptoms, positive symptoms, and cognitive dysfunction. The outcomes of studies on the role of microglia and neuroinflammation have been conflicting. In addition, there is a poor understanding of the sex differences in microglial expression and neuroinflammation markers in the prefrontal cortex, hippocampus, and nucleus accumbens. Understanding the exact roles of neuroinflammation may guide the development of efficient therapeutic drugs that can address the negative, positive, and cognitive symptoms of the disease. We examined the effect of social isolation rearing on schizophrenia-related behaviours in male and female BALB/c mice. The social-isolation rearing protocol started on post-natal day (PND) 21, lasting for 35 days. Animals were assigned to four cohorts, consisting of five animals per group. On PND 56, animals were assessed for behavioural changes. We used enzyme-linked immunosorbent assays to investigate the expression of nuclear factor kappa B (NF-κB), tumour necrosis factor-α (TNF-α), and Interleukin-1ß (IL-1ß) in the hippocampus, nucleus accumbens, and prefrontal cortex. Immunohistochemistry was used to assess the expression of microglia in the three brain regions. Our study showed that isolation rearing led to increasing locomotion, heightened anxiety, depression, and a reduced percentage of prepulse inhibition. There was a significant increase (p < 0.05) in anxiety in the female isolation mice compared to male isolation mice. Furthermore, isolation rearing significantly increased microglia count (p < 0.05) in the hippocampus, nucleus accumbens, and prefrontal cortex, only in the male group. There was microglial hyper-activation as evident in the downregulation of CX3CR1 in both male and female social-isolation groups. Male social-isolation mice showed a significant increase (p < 0.05) in neuroinflammation markers only in the nucleus accumbens while the female social-isolation mice showed a significant increase (p < 0.05) in neuroinflammation markers in both the nucleus accumbens and hippocampus. The study showed that therapeutic interventions aimed at modulating CX3CR1 activity and reducing inflammation may be beneficial for patients with schizophrenia.

Effect Of Caffeine and Adrenaline on Memory and Anxiety in Male Wistar Rats.

The present study was designed to investigate the effects of caffeine and adrenaline administration on memory and anxiety in male rats. Rats weighing about 140-200g were used for the study. They were divided into three groups (4 animals per group). Study groups 1; a,b,c,d were healthy rats administered normal saline, 5,10 and 15mg/kg bw caffeine intraperitoneally (i.p.), respectively for 6 weeks. Study groups 2; a,b,c,d administered normal saline, 0.1, 0.2 and 0.31mg/kg bw adrenaline (i.p.), respectively for 6 weeks. Study groups 3; a,b,c,d administered normal saline, 5mg/kg caffeine (i.p.) + 0.1mg/kg adrenaline (i.p.), 10mg/kg Caffeine (i.p.) + 0.2mg/kg Adrenaline (i.p.) and 15mg/kg Caffeine (i.p.) + 0.3mg/kg Adrenaline (i.p.) respectively for 6 weeks. The result showed no significant difference in spatial memory across all animals in study groups 1: b,c,d when compared to control (a). Study groups 2: (b, c) showed increase in spatial memory when compared to control (a). 2(d) showed a significant (p<0.05) decrease. Study groups 3: b, c, d showed no significant difference in spatial memory when compared to control (a). Study groups 1: b, c showed significant (p<0.05) reduction in duration for the short and long term memory test when compared to control. Study groups 2 showed reduction in duration for both the long and short term memory test when compared to control Study groups 3 no significant (p<0.05) difference in short and long term memory test across all animals in the group. It was also observed that adrenaline enhanced short and long term memory and only high dose of adrenaline distorted spatial memory. Study groups 1; (b,c) showed significant (p<0.05) increase in the number of entries to the open arm of the elevated plus maze when compared to control (a). Study groups 2; (b), showed significant (p<0.05) increase in the frequencies of entries to the closed arm of the elevated plus maze when compared to control (a). Study groups 2; (d), showed a significant (p<0.05) decrease in the frequency of entries to the open and closed arm when compared to control (a). The study revealed that co- administration of caffeine and adrenaline led to elevation of mood, increased activity and reduction of anxiety in Wistar rats. In addition, it was observed that only high dose of adrenaline increased anxiety. It was also observed that caffeine and adrenaline enhanced short and long term memory and only high dose of adrenaline distorted spatial memory.

Synergistic interaction between acetaminophen and L-carnosine improved neuropathic pain via NF-κB pathway and antioxidant properties in chronic constriction injury model.

Background: Inflammation is known to underlie the pathogenesis in neuropathic pain. This study investigated the anti-inflammatory and neuroprotective mechanisms involved in antinociceptive effects of co-administration of acetaminophen and L-carnosine in chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. Methods: Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8) treated with normal saline/acetaminophen/acetaminophen + L-carnosine. CCI was used to induce neuropathic pain in rats. Hyperalgesia and allodynia were assessed using hotplate and von Frey tests, respectively. Investigation of spinal proinflammatory cytokines and antioxidant system were carried out after twenty-one days of treatment. Results: The results showed that the co-administration of acetaminophen and L-carnosine significantly (P < 0.001) increased the paw withdrawal threshold to thermal and mechanical stimuli in ligated rats compared to the ligated naïve group. There was a significant (P < 0.001) decrease in the levels of nuclear factor kappa light chain enhancer B cell inhibitor, calcium ion, interleukin-1-beta, and tumour necrotic factor-alpha in the spinal cord of the group coadministered with acetaminophen and L-carnosine compared to the ligated control group. Co-administration with acetaminophen and L-carnosine increased the antioxidant enzymatic activities and reduced the lipid peroxidation in the spinal cord. Conclusions: Co-administration of acetaminophen and L-carnosine has anti-inflammatory effects as a mechanism that mediate its antinociceptive effects in CCI-induced peripheral neuropathy in Wistar rat.

Therapeutic effects of crude extracts of Bacopa floribunda on beta-amyloid 1-42-induced Alzheimer's disease via suppression of dyslipidemia, systemic inflammation and oxidative stress in male Wistar Rats.

Aims: Bacopa floribunda (BF), an African traditional plant and its species have been widely used as brain tonic for memory enhancement. It has also been reported to help relieve anxiety and some psychological disorders. This study aimed to investigate the mechanisms of action of BF on Amyloid beta (Aß) 1-42 peptides induced cognitive deficit in male Wistar rats. Main methods: A total of 48 healthy male wistar rats were used for this study. Some groups were pre-treated with 200 mg/kg of BF extracts before a single bilateral injection of Aß 1-42 while some were post-treated with BF for 21 days after Aß1-42 exposure. Cognitive performance was evaluated using Y-Maze and Novel Object recognition tests. After treatments, hippocampal homogenates were assayed for the levels of Acetylcholinesterase, Na-K/ATPase activities, glutamate and Aß1-42 concentrations among others. Key findings: It was observed that Aß1-42 caused cognitive impairment and BF extracts especially the ethanol extract was able to significantly (p < 0.05) reverse almost all the perturbations including lipid imbalance caused by Aß1-42 assault mainly at the post-treatment level. Significance: Administration of ethanol and aqueous extracts of BF mitigated the hazardous effect of Aß1-42 observed in the blood plasma and hippocampal homogenates. In this context, we conclude that BF is an efficient cognitive enhancer that can help alleviate some symptoms associated with Alzheimer's disease.

Chondroitin and glucosamine sulphate reduced proinflammatory molecules in the DRG and improved axonal function of injured sciatic nerve of rats.

Neuropathic pain (NP) is an abnormality resulting from lesion or damage to parts of the somatosensory nervous system. It is linked to defective quality of life and often poorly managed. Due to the limited number of approved drugs, limited efficacy and side effects associated with the approved drugs, drugs or drug combinations with great efficacy and very minimal or no side effects will be of great advantage in managing NP. This study aimed at investigating the synergistic antinociceptive effects of the combination of glucosamine sulphate (GS) (240 mg/kg) and chondroitin sulphate (CS) (900 mg/kg) in chronic constriction injury (CCI)-induced neuropathy in rats. Forty-two Wistar rats were randomly distributed into seven groups (n = 6). Sciatic nerve was ligated with four loose ligatures to induce NP. Effects of drugs were examined on stimulus and non-stimulus evoked potentials, expression of dorsal root ganglia (DRG) pain modulators and structural architecture of DRG. Oral administration of GS and CS for 21 days reduced hyperalgesia, allodynia, sciatic nerve functional aberration and DRG pain modulators. Histopathology and immunohistochemistry revealed restoration of structural integrity of DRG. Our result showed that the combination of GS and CS produced antinociceptive effects by attenuating hyperalgesia, allodynia and downregulation of NP mediators. GS and CS additionally produced synergistic analgesic effect over its individual components.

Saponins and flavonoids from Bacopa floribunda plant extract exhibit antioxidant and anti-inflammatory effects on amyloid beta 1-42-induced Alzheimer's disease in BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa floribunda (BF), a locally available plant has been employed traditionally as memory enhancer in Southwestern, Nigeria. It has been utilized in traditional and Ayurvedic medicine as brain tonic for enhancing memory, anti-aging and forestalling series of psychological disorders. However, there is a dearth of scientific information on the mechanism(s) of action of important phytochemicals from BF extract on dementia. AIM OF THE STUDY: Alzheimer's disease, the commonest form of dementia has been postulated to triple by 2050 as a result of increase in life expectancy. This study therefore assessed and compared the possible mechanism(s) of action of flavonoids and saponins from BF on Amyloid beta (Aß1-42)-induced dementia in male BALB/c mice. MATERIALS AND METHODS: Eighty (80) healthy BALB/c mice divided into 10 groups (n = 8) were given a single bilateral ICV injection of Aß1-42 or normal saline. Graded doses of Saponins and flavonoids (50, 100 and 200 mg/kg) were used as treatment for 21 days. Hippocampal homogenates were assayed for the levels of antioxidants, oxidative stress and neuroinflammatory markers. In vitro antioxidant activity of flavonoids and saponins were equally assessed using standard procedures. The extent of microglial activation was quantified through immunohistochemistry procedure. RESULTS: Aß1-42 successfully caused a spike in hippocampal levels of MDA, IL1ß, TNF-α including MPO levels and invariably decreased antioxidant activities. Likewise an increase in reactive microglia (microgliosis) was observed. However, crude saponins and flavonoids from BF were able to suppress microgliosis, oxidative stress and neuroinflammation induced by Aß1- 42 and were observed to be more effective at higher doses of saponins (100 mg/kg and 200 mg/kg) and flavonoid (100 mg/kg). CONCLUSIONS: Phytochemicals from BF efficiently exhibited dose dependent alleviation of some symptoms associated with Alzheimer's disease.

Vitamin D attenuated 6-OHDA-induced behavioural deficits, dopamine dysmetabolism, oxidative stress, and neuro-inflammation in mice.

Background: L-DOPA, the predominant therapy for Parkinson's disease (PD) is associated with motor deficits after prolonged use. The nigrostriatal tract, a primary target of neurodegeneration in PD, contains abundant Vitamin-D receptors, suggesting a potential role for VD in the disease. Therefore, we tested the impact of Vitamin D3 (VD3) in a mouse model of PD.Methods: PD was induced in adult male C57BL6 mice by a single intrastriatal injection of 6-hydroxydopamine. Two weeks post lesion, these mice received injections of a vehicle, VD3, L-DOPA, or a combination of VD3/L-DOPA and compared with sham controls. Treatment lasted three weeks, during which motor-cognitive neurobehaviour was assessed. Five weeks post lesion, brains were collected and striatal levels of the following proteins assessed: tyrosine hydroxylase (TH), dopamine decarboxylase (DDC), monoamine oxidase (MAO-B), Catechol-O-methyl transferase (COMT), dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), microglia marker (CD11b), inflammation (IL-1ß), apoptotic signaling (BAX) and oxidative stress (p47phox).Results: Treatment with VD3 attenuated behavioural deficits induced by 6-OHDA, protein associated with dopamine metabolism and biomarkers of oxidative stress. VD3 significantly increased contralateral wall touches, exploratory motor and cognitive activities. VD3 significantly enhanced the expression of TH, DAT, BDNF, while significantly reducing expression of MAO-B, CD11b, IL-I ß and p47phox.Conclusion: VD3 reversed some of the 6-OHDA induced changes in proteins involved in modulating the dopamine system, behavioural deficits and oxidative stress biomarkers. The data suggests that VD3 might be beneficial in reducing L-DOPA dosage, thereby reducing problems associated with dosage and prolonged use of L-DOPA in PD management.

Effects of co-administration of vitamin E and lithium chloride on chronic constriction injury-induced neuropathy in male Wistar rats: Focus on antioxidant and anti-inflammatory mechanisms.

OBJECTIVES: This study investigated the antinociceptive effects of co-administration of lithium chloride (LiCl) and vitamin E (Vit E) on chronic constriction injury (CCI)-induced peripheral neuropathy in male Wistar rats. It further explored the anti-inflammatory and neuroprotective properties of LiCl and Vit E, which may be complementary to the antinociceptive effects of the two substances. METHODS: Thirty-six male Wistar rats, 190.00 ± 10.00 g of body weight were randomly assigned to 6 experimental groups and administered with normal saline, Vit E, LiCl, or their combination, once daily for 21 days. CCI was used to induce neuropathic pain (NP) and mechanical allodynia was assessed using von Frey filaments and pinprick test. Open field maze (OFM) was used to assess the exploratory behavior. Biochemical parameters were assessed in the dorsal root ganglion after 21 days of treatment. RESULTS: Mechanical allodynia was developed in rats following CCI. Co-administration of LiCl and Vit E synergistically reduced mechanical hyperalgesia in rats which were significantly different compared with the single administration of either Vit E or LiCl. Combined doses of Vit E and LiCl significantly increases the explorative behavior in the OFM. CCI increased malondialdehyde (MDA), tumor necrotic factor-alpha (TNF-α), calcitonin gene-related polypeptide, calcium ion (Ca2+ ), and reduced superoxide dismutase (SOD) activities. Co-administration of LiCl and Vit E significantly reduced MDA, TNF-α, but increased SOD compared with ligated control. DISCUSSION: The findings revealed that the synergistic effects of the co-administration of Vit E and LiCl in ameliorating NP are mediated by their anti-inflammatory and antioxidant properties.

Selenium reduces nociceptive response in acute 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced neurotoxicity.

The potential of Se to alleviate pain associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity was investigated. Swiss mice were intraperitoneally injected with MPTP (20 mg/kg) 4 times with an interval of 2 h in 1 day. Seven days after MPTP injection, the mice (n = 5 mice per group) were randomly assigned to groups: MPTP-, DOPA (50 mg/kg)-, Se4 (0.4 mg/kg)-, Se6 (0.6 mg/kg)-, DOPA+Se4-, and DOPA+Se6-treated groups were compared with controls. MPTP mice were treated for seven days; thereafter, motor-coordination and nociceptive-motor reactions were assessed. Pro-inflammatory cytokines (IL-1ß, IL-6 and TNFα), and selected pain biomarkers (substance P (SP), glutamate and ß-endorphin) were assessed in the serum and the substantial nigra pars compacta (SNpc). Motor activity was increased slightly by Se (0.6 or 0.4 mg/kg) vs. MPTP (10.48 ± 2.71 or 11.81 ± 1.28 s vs. 3.53 ± 0.06 s respectively) but considerably increased by DOPA (50 mg/kg) vs. MPTP (50.47 ± 3.06 s vs. 3.53 ± 0.06 s respectively). Se and DOPA increased nociceptive threshold but Se alone reduced both serum and SN pro-inflammatory cytokines. Se modulates SP while DOPA modulates SP and glutamate in the SNpc of mice treated with MPTP. Se suppressed pro-inflammatory cytokines and restored the basal pain biomarkers in the SNpc of mice treated with MPTP. Se requires further study as analgesic adjuvant.

Cholecalciferol (VD3) Attenuates L-DOPA-Induced Dyskinesia in Parkinsonian Mice Via Modulation of Microglia and Oxido-Inflammatory Mechanisms.

L-DOPA, the gold standard for managing Parkinson's disease (PD) is fraught by motor fluctuations termed L-Dopa-Induced Dyskinesia (LID). LID has very few therapeutic options. Hence, the need for preclinical screening of new interventions. Cholecalciferol (VD3) treatment reportedly improves motor deficit in experimental Parkinsonism. Therefore, the novel anti-dyskinetic effect of VD3 and its underlying mechanisms in LID was investigated. Dyskinesia was induced by chronic L-DOPA administration in parkinsonian (6-OHDA- lesioned) mice. The experimental groups: Control, Dyskinesia, Dyskinesia/VD3, and Dyskinesia/Amantadine were challenged with L-DOPA to determine the abnormal involuntary movements (AIMs) score during 14 days of VD3 (30 mg/kg) or Amantadine (40 mg/kg) treatment. Behavioral Axial, Limb & Orolingual (ALO) AIMs were scored for 1 min at every 20 mins interval, over a duration of 100 mins on days 1,3,7,11 and 14. Using western blot, striatum was assessed for expression of dopamine metabolic enzymes: Tyrosine Hydroxylase (TH) and Monoamine Oxidase-B (MAO-B); CD11b, BAX, P47phox, and IL-1ß. Cholecalciferol significantly attenuated AIMs only on days 11 & 14 with maximal reduction of 32.7%. Expression of TH and MAO-B was not altered in VD3 compared with dyskinetic mice. VD3 significantly inhibited oxidative stress (P47phox), apoptosis (BAX), inflammation (IL-1ß) and microglial activation (CD11b). VD3 showed anti-dyskinetic effects behaviorally by attenuating abnormal involuntary movements, modulation of striatal oxidative stress, microglial responses, inflammation, and apoptotic signaling; without affecting dopamine metabolic enzymes. Its use in the management of dyskinesia is promising. More studies are required to further evaluate these findings. Keywords: Cholecalciferol; L-DOPA-Induced Dyskinesia; Parkinson's Disease; Microglial; Oxidative stress; Inflammation.

Streptozotocin-induced type 1 and 2 diabetes in rodents: a model for studying diabetic cardiac autonomic neuropathy.

BACKGROUND: Several animal models are continually being developed to study diabetic complication. Several conflicting regimen for diabetes induction exist in the literature with varying dose strength and regimen for different study interest in diabetes. This study aims to show the effect of high dose streptozotocin (STZ) on the one hand compared with multiple low doses after high fat diet induction on diabetic cardiac autonomic neuropathy (DCAN). METHODOLOGY: Eighty-four Wistar rats were used to demonstrate DCAN induction using 2 approaches one for T1DM (STZ 50mg/kg) and the other for T2DM (HFD for 8 weeks with STZ 25mg/Kg daily for five days). DCAN features were assessed using invasive biomarkers, histology patterns and cardiac nerve densities. RESULTS: Diabetes induction rate was 76% and 89% in T1DM and T2DM model respectively. T1DM group had significant weight loss, reduced c-peptide, and insulin level post induction. The T2DM additionally showed significantly higher total cholesterol and Homeostatic model assessment (HOMA) compared with control. Serum levels of catecholamine, choactase, nerve growth factor and cardiac nerve density confirms development of DCAN. CONCLUSION: High single dose of STZ and HFD with multiple low doses of STZ may be recommended for DCAN study in T1DM and T2DM rat model respectively.

Chondroitin sulfate produces antinociception and neuroprotection in chronic constriction injury-induced neuropathic pain in rats by increasing anti-inflammatory molecules and reducing oxidative stress.

OBJECTIVES: Damage to the peripheral and central nervous system lead to Neuropathic pain (NP) which is a widespread and devitalizing condition. chondroitin sulfate (CS), has been used in managing joint pain and osteoarthritis. In this study, the effectiveness of CS on NP induced by chronic constriction injury (CCI) is examined. METHODS: Thirty Wistar rats were distributed at random into six groups (n = 5). Sciatic nerve ligation was carried out by encircling the nerve with four loose ligatures to induce NP. Allodynia (cold and mechanical) and heat hyperalgesia were assessed using Acetone, von Frey filament and Hot plate tests. CCI induction resulted to NP, prominent from the 3rd day after surgery. Structural architecture of sciatic nerves was evaluated via histological examination of the transverse section of the nerves. RESULTS: Oral administration of CS (600 mg/kg and 900 mg/kg for 21 days) resulted in significant (P < 0.05) inhibition of allodynia (cold and mechanical) and thermal hyperalgesia. Lipid peroxidation, tumor necrosis factor-α (TNF-α), calcitonin gene related peptide (CGRP), C reactive protein (CRP), and oxidative stress were attenuated by CS. CS also improved interleukin (IL)-6, nitric oxide (NO), total antioxidant capacity (TAC). CONCLUSION: These findings suggest that CS attenuates allodynia, and thermal hyperalgesia induced by CCI by downregulating TNF-α, CRP, CGRP, oxidative enzymes, and upregulating IL-6, NO, and TAC. Nociceptive behavioral studies and histological findings showed significant improvement in the CS treated groups compared to CCI rats. These findings are responsible for the beneficial effect of CS in NP.

Antinociceptive effects of lead acetate in sciatic nerve chronic constriction injury model of peripheral neuropathy in male Wistar rats.

The toxicological effects of lead and its compounds have overshadowed its possible health beneficial effects. Currently, the success rate for treating neuropathic pain has been very low. This study investigated the antinociceptive effects of orally administered low dose lead acetate in sciatic nerve ligated Wistar rats. Thirty Wistar rats randomly divided into five groups were used for this study. Chronic constriction injury (CCI) was used to induce neuropathic pain in Wistar rats. Allodynic and hyperalgesic signs were investigated using von Frey filaments and hotplate, respectively. Morris water maze test was used to assess the memory functions of the rats. The study revealed that oral administration of low-dose lead acetate significantly (p < 0.05) increased pain thresholds of ligated rats. CCI enhanced memory function in Wistar rats which was significantly decreased following lead acetate administration. The findings suggest that lead acetate possesses antinociceptive effects in peripherally induced neuropathic pain model in Wistar rats.

Heart rate variability indices, biomarkers, and cardiac nerve density: Independent surrogate markers for diagnosis of diabetic cardiac autonomic neuropathy in type 2 diabetes mellitus animal model.

OBJECTIVES: Heart rate variability (HRV) has been shown to represents a promising quantitative marker of autonomic activity. Studies have shown that diabetic patients and animal models have derangements in certain biochemical parameters with reduced cardiac nerve density following development of diabetic cardiac autonomic neuropathy (DCAN). This study, therefore, aims to correlate HRV indices, cardiac histology, and cardiac nerve density with selected biochemical markers in the DCAN rat model using high fat diet (HFD) and streptozotocin (STZ) induction. METHODS: DCAN was induced in Wistar rats using HFD for 8 weeks with 25 mg/kg STZ daily for 5 days. DCAN features were then assessed using Holter electrocardiography (ECG), invasive biomarkers, and cardiac histology. RESULTS: DCAN group had significantly higher advanced glycated end product levels (P < 0.0001), noradrenaline (P = 0.010), and insulin resistance (P = 0.016) compared with controls. The level of antioxidants, sorbitol dehydrogenase activity (P = 0.009), nerve growth factors (P < 0.0001), and choline acetyl-transferase (P = 0.031) was, however, significantly reduced. Furthermore, HRV indices which were also reduced with DCAN induction correlated significantly with levels of biomarkers and cardiac nerve density. CONCLUSION: HRV is a cheap and easy tool for assessing DCAN that significantly correlates with markers of autonomic activity. Holter ECG and HRV evaluation should be considered early in patients with diabetes.

Antinociceptive and neuroprotective effects of bromelain in chronic constriction injury-induced neuropathic pain in Wistar rats.

BACKGROUND: The continuous search for a novel neuropathic pain drug with few or no side effects has been a main focus of researchers for decades. This study investigated the antinociceptive and neuroprotective effects of bromelain in sciatic nerve ligation-induced neuropathic pain in Wistar rats. METHODS: Forty-eight Wistar rats randomly divided into eight groups comprised of six animals each were used for this study. Peripheral neuropathy was induced via chronic constriction of the common sciatic nerve. Thermal hyperalgesic and mechanical allodynia were assessed using a hotplate and von Frey filaments, respectively. The functional recovery and structural architecture of the ligated sciatic nerve were evaluated using the sciatic functional index test and a histological examination of the transverse section of the sciatic nerve. The neuroprotective effects of bromelain were investigated in the proximal sciatic nerve tissue after 21 days of treatment. RESULTS: Bromelain significantly (P < 0.05) attenuated both the thermal hyperalgesia and mechanical allodynic indices of neuropathic pain. There were improvements in sciatic function and structural integrity in rats treated with bromelain. These rats showed significant (P < 0.05) increases in sciatic nerve nuclear transcription factors (nuclear factor erythroid-derived-2-related factors-1 [NrF-1] and NrF-2), antioxidant enzymes (superoxide dismutase and glutathione), and reduced membrane-lipid peroxidation compared with the ligated control group. CONCLUSIONS: This study suggest that bromelain mitigated neuropathic pain by enhancing the activities of nuclear transcription factors (NrF-1 and NrF-2) which increases the antioxidant defense system that abolish neuronal stress and structural disorganization.

Bromelain reversed electrolyte imbalance in the chronically constricted sciatic nerve of Wistar rats.

Derangement of electrolyte in the sensory nervous system has been attributed to the development and maintenance of hyperalgesic and allodynic symptoms in painful neuropathy. This study investigated the effect of bromelain on electrolyte imbalance in chronically constricted sciatic nerve of rats (a model of neuropathic pain). Forty Wistar rats, divided into five groups of eight animals each were used for this study. von Frey filaments, tail immersion and acetone spray tests were used to assessed allodynic and thermal hyperalgesic symptoms in the Wistar rats. Sodium ion (Na+), potassium ion (K+), calcium ion (Ca2+) and chloride ion (Cl-) concentrations as well as sodium-potassium and calcium electrogenic pump (Na-K ATPase and Ca ATPase, respectively) activities were estimated using spectrophotometry techniques. Bromelain significantly (p < 0.05) reversed elevation of Na+ and Ca2+ concentration compared with sciatic nerve chronic constriction injury (snCCI) group (35.68 ± 1.71 vs 44.46 ± 1.24 mg/ml/mg protein and 1.06 ± 0.19 vs 6.66 ± 0.03 mg/ml/mg protein, respectively). There were also significant (p < 0.05) increases in the level of K+ (0.84 ± 0.02 vs 0.36 ± 0.05 mg/ml/mg protein) and Cl- (18.51 ± 0.29 vs 15.82 ± 0.21 mg/ml/mg protein). Bromelain reduced the activities of Ca2+ electrogenic pumps significantly compared with snCCI. This study therefore suggests that bromelain mitigated electrolyte imbalance in chronic constricted injury of the sciatic nerve implying that this may be an important mechanism for the anti-nociceptive effect of bromelain.

Coconut oil protects against light-induced retina degeneration in male Wistar rats.

The retinoprotective effect of Cocos nucifera oil (CNO) was investigated. Twenty male Wistar rats weighing 140 g and 180 g were randomly divided into four groups comprising of five animals each. The control group received distilled water. Retinal degeneration was induced in the remaining three groups by exposing the animals to 5,000 lux of bright white light for two hours. Prior to the light exposure, the light model group (LMG) received distilled water for 14 days, low Cocos nucifera oil (LCNO) group received 5 ml/kg of CNO for 14 days, and the high Cocos nucifera oil (HCNO) group received 10 ml/kg of CNO for 14 days. The treatments continued for 7 days after exposure to light. On the eight day, the animals were euthanised and their retinas isolated. The right retinas and occipital cortices of the animals were prepared for histological evaluation while the homogenates of the left retinas were used for biochemical assay. The results show that CNO significantly (p < 0.05) reduced caspase-3 activity from 1.15 ± 0.054 ng/ml to 0.434 ± 0.095 ng/ml (LMG versus LCNO) and malondialdehyde concentration. There was no significant difference in the total antioxidant capacity in the retinas of the rats. However, LMG showed a significant increase in catalase activity. CNO was able to preserve the retinal morphology while LMG showed a distorted retinal layer and significant reduction (p < 0.05) in retina thickness. CNO was unable to prevent perineural vacuolations in the occipital cortices of the rats. In conclusion, Cocos nucifera oil produced retino-protective effect via anti-oxidative and anti-apoptotic mechanisms.

Effects of acetone extract of Cola nitida on brain sodium-potassium adenosine triphosphatase activity and spatial memory in healthy and streptozotocin-induced diabetic female Wistar rats.

Background This study was carried out to investigate the effects of acetone extract of Cola nitida on brain Na+/K+-ATPase activity and spatial memory of healthy and streptozotocin (STZ)-induced diabetic female Wistar rats. Methods Forty-two female Wistar rats were used for this study and were randomly distributed into six groups (n=7). Rats in group 1 were used as control and were administered normal saline; group 2 rats were healthy rats administered 50 mg/kg of kola nut extract per day; group 3 rats were healthy rats administered 100 mg/kg of kola nut extract per day; group 4 rats were a diabetic group also administered normal saline; group 5 rats were diabetic rats administered 50 mg/kg of kola nut extract per day; and group 6 rats were diabetic rats administered 100 mg/kg of kola nut extract per day. Diabetes was induced with 50 mg/kg of STZ. After 3 weeks of administration, the spatial memories of the rats were tested using the Y-maze, followed by assay of Na+/K+-ATPase activity. Results The result shows a significant increase in Na+/K+-ATPase activity of diabetic treated groups (5 and 6) when compared with the diabetic group (4) and a significant increase in Na+/K+-ATPase activity of healthy treated groups (2 and 3) when compared with control. Also, there was a significant increase in spatial memory of the diabetic treated groups when compared with diabetic group. Conclusions This study revealed that kola nut extract has restorative effect on brain Na+/K+-ATPase activities and spatial memory of STZ-induced diabetic female Wistar rats.