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Old age is associated with enhanced susceptibility to and poor recovery from brain injury. An exacerbated microglial and astrocyte response to brain injury might be involved in poor outcomes observed in the elderly. The present study was therefore designed to quantitate the expression of markers of microglia and astrocyte activation using real-time RT-PCR, immunoblot and immunohistochemical analysis in aging brain in response to brain injury. We examined the hippocampus, a region that undergoes secondary neuron death, in aged (21-24 month) and adult (5-6 month) mice following controlled cortical impact (CCI) injury to the sensorimotor cortex. Basal mRNA expression of CD11b and Iba1, markers of activated microglia, was higher in aged hippocampus as compared to the adult. The mRNA expression of microglial markers increased and reached maximum 3 days post injury in both adult and aged mice, but was higher in the aged mice at all time points studied, and in the aged mice the return to baseline levels was delayed. Basal mRNA expression of GFAP and S100B, markers of activated astrocytes, was higher in aged mice. Both markers increased and reached maximum 7 days post injury. The mRNA expression of astrocyte markers returned to near basal levels rapidly after injury in the adult mice, whereas again in the aged mice return to baseline was delayed. Immunochemical analysis using Iba1 and GFAP antibodies indicate accentuated glial responses in the aged hippocampus after injury. The pronounced and prolonged activation of microglia and astrocytes in hippocampus may contribute to worse cognitive outcomes in the elderly following TBI.

BackgroundPhytochemicals like carotenoids, tocopherols, ascorbates and phenols present in the plants are strong antioxidants and have an important role in the health care system. There is growing interest in correlating the phytochemical constituents of a plant with its pharmacological activity. Therefore, the present study investigates the content of total phenolics, flavonoids and the antioxidant activity of four different varieties of Lantana camara L. (Verbenaceae) leaves by using in vitro antioxidant models.MethodsThe leaves of Chandigarh purple variety (CPV), Palampur red variety (PRV), Chandigarh yellow turning pink variety (YTPV) and Chandigarh yellow variety (CYV) Lantana camara were collected and the total phenolic, flavonoid content, antioxidant and free radical scavenging activities were determined in their methanolic extracts.ResultsThe phenolic content was found to be highest in the CYV extract (232.99 ± 15.97 mg GAE/ g extract). The content of the flavonoids are in the order of YTPV, PRV, CPV and CYV. The IC50 values for the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging test were in the order of CYV (33.30 ± 2.39) < PRV (40.32 ± 2.94) < YTPV (475.33 ± 5.20) < CPV (927.16 ± 2.88 μg/mL). The highest total antioxidant capacity was observed in CYV (222.20 ± 5.05 mg AAE/ g). The Ferric ion reducing antioxidant potential (FRAP) value of the extracts were in the order of CYV > PRV > YTPV > CPV. The IC50 values of 2, 2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonate) (ABTS) scavenging assay for CYV, PRV, YTPV, CPV were 18.25 ± 0.19, 18.24 ± 1.82, 50.43 ± 9.49, 52.84 ± 1.82 μg/mL respectively. PRV extract showed the maximum in vitro lipid peroxidation inhibition effect with an IC50 value of 68.50 μg/mL which is even stronger as compared to the standard Rutin (79.69 μg/mL). The extracts showed a strong correlation between the phenolic content and their antioxidant activities. The highest correlation (r = 0.998, R2 = 0.997) was found between total phenolic content and ABTS scavenging assay.ConclusionAmong the four varieties investigated, CYV and PRV extracts showed strong antioxidant activities and may be used as a potential source of natural antioxidant against free radical associated diseases.

We have investigated the effect of lead exposure on lipid peroxidation, a deteriorative process of the membranes, in the different regions of the brain. Lead treatment (50 mg/kg b.wt. intragastrically) for a period of eight weeks to rats resulted in a significant accumulation of lead in all the regions of brain, at maximum in hippocampus. The lipid peroxidation was accentuated following lead exposure and there was a linear correlation between the increase in lipid peroxidation and increase in lead levels (r = 0.75). The antioxidant capacity of the neuronal cells in terms of the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase was diminished. Lead treatment also altered the glutathione status i.e. levels of reduced glutathione were lowered, accompanied with the accumulation of oxidized glutathione. Furthermore, the activity of glutathione reductase was significantly lowered in lead-treated animals. The activity of membrane bound enzyme acetylcholinesterase was significantly inhibited following lead exposure and there was a linear correlation between the increase in lipid peroxidation and decrease in acetylcholinesterase activity (r = -0.83). It appears from the results that lead may exert its neurotoxic effects via peroxidative damage to the membranes.

Till date, an exact causative pathway responsible for neurodegeneration in Huntington's disease (HD) remains elusive; however, mitochondrial dysfunction appears to play an important role in HD pathogenesis. Therefore, strategies to attenuate mitochondrial impairments could provide a potential therapeutic intervention. In the present study, we used curcumin encapsulated solid lipid nanoparticles (C-SLNs) to ameliorate 3-nitropropionic acid (3-NP)-induced HD in rats. Results of MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and succinate dehydrogenase (SDH) staining of striatum revealed a marked decrease in Complex II activity. However, C-SLN-treated animals showed significant increase in the activity of mitochondrial complexes and cytochrome levels. C-SLNs also restored the glutathione levels and superoxide dismutase activity. Moreover, significant reduction in mitochondrial swelling, lipid peroxidation, protein carbonyls and reactive oxygen species was observed in rats treated with C-SLNs. Quantitative PCR and Western blot results revealed the activation of nuclear factor-erythroid 2 antioxidant pathway after C-SLNs administration in 3-NP-treated animals. In addition, C-SLN-treated rats showed significant improvement in neuromotor coordination when compared with 3-NP-treated rats. Thus, the results of this study suggest that C-SLNs administration might be a promising therapeutic intervention to ameliorate mitochondrial dysfunctions in HD.

Estrogen increases facial allodynia through its actions on activation of the MAP kinase ERK in trigeminal ganglion neurons. This goal of study was to determine which estrogen receptor is required for behavioral sensitization. Immunohistochemical studies demonstrated the presence of estrogen receptor alpha (ERα) in nuclei of larger neurons and cytoplasm of smaller neurons, and the novel estrogen receptor G-protein coupled receptor 30 (GPR30) in small diameter neurons that also contained peripherin, a marker of unmyelinated C-fibers. Specific agonists for ERα (PPT) and GPR30 (G-1), but not ERβ (DPN), activated ERK in trigeminal ganglion neurons in vitro. Both G-1 and PPT treatment increased allodynia after CFA injections in to the masseter of ovariectomized Sprague-Dawley rats. Treatment with estrogen increased expression of ERα but not GPR30, while masseter inflammation increased GRP30 but not ERα. Differential modulation of these ERK-coupled receptors by estrogen and inflammation may play a role in painful episodes of TMD and migraine.

The present study was undertaken to understand the biochemical mechanisms of lead toxicity in liver. We observed a significant accumulation of lead in liver following lead treatment, resulting in accentuation of lipid peroxidation. Concomitant to the increase in lipid peroxidation, the activities of antioxidant enzymes, viz., superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, were significantly inhibited. A decrease in reduced glutathione with a simultaneous increase in oxidized glutathione was observed following lead exposure, resulting in a reduced GSH/GSSG ratio. These results indicate that lead exerts its toxic effects by enhancing peroxidative damage to the membranes, thus compromising cellular functions.

Evidence from clinical and experimental studies indicate that oxidative stress is involved in pathogenesis of Parkinson's disease. The present study was designed to investigate the neuroprotective potential of lycopene on oxidative stress and neurobehavioral abnormalities in rotenone induced PD. Rats were treated with rotenone (3 mg/kg body weight, intraperitoneally) for 30 days. NADH dehydrogenase a marker of rotenone action was observed to be significantly inhibited (35%) in striatum of treated animals. However, lycopene administration (10 mg/kg, orally) to the rotenone treated animals for 30 days increased the activity by 39% when compared to rotenone treated animals. Rotenone administration increased the MDA levels (75.15%) in striatum, whereas, lycopene administration to rotenone treated animals decreased the levels by 24.33%. Along with this, significant decrease in GSH levels (42.69%) was observed in rotenone treated animals. Lycopene supplementation on the other hand, increased the levels of GSH by 75.35% when compared with rotenone treated group. The activity of SOD was inhibited by 69% in rotenone treated animals and on lycopene supplementation; the activity increased by 12% when compared to controls. This was accompanied by cognitive and motor deficits in rotenone administered animals, which were reversed on lycopene treatment. Lycopene treatment also prevented release of cytochrome c from mitochondria. Collectively, these observations suggest that lycopene supplementation along with rotenone for 30 days prevented rotenone-induced alterations in antioxidants along with the prevention of rotenone induced oxidative stress and neurobehavioral deficits. The results provide an evidence for beneficial effect of lycopene supplementation in rotenone-induced PD and suggest therapeutic potential in neurodegenerative diseases involving accentuated oxidative stress.