Bell's palsy is a common neurological problem causing considerable loss of self-esteem among patients. A prospective observational study was conducted to determine the short-term outcome of Bell's palsy at 1 month and 2 months after the onset and the relationship between these outcomes with facial nerve degeneration. We also determined if gender, age, diabetes, systolic and diastolic blood pressure influence the severity of facial nerve degeneration and the clinical outcome at 2 months after the onset. After clinically grading the newly diagnosed unilateral Bell's palsy patients using the House-Brackmann facial nerve grading system, nerve conduction studies of the facial nerve were done to determine the severity of facial nerve degeneration. The recovery of the facial paralysis was clinically graded again at the end of 1 month and 2 months from the onset. A total of 37 patients were recruited. There was a strong positive correlation between facial nerve degeneration and the clinical outcome of Bell's palsy at 1 month (r = 0.794; p < 0.0005) and 2 months (r = 0.732; p < 0.0005) after the onset. There was no significant correlation between either the facial nerve degeneration or the clinical outcome at 2 months with the patients' age (p = 0.288 and p = 0.799 respectively), systolic blood pressure (p = 0.425 and p = 0.933 respectively) or diastolic blood pressure (p = 0.243 and p = 0.579 respectively). Neither the severity of facial nerve degeneration nor the clinical outcome at 2 months were significantly different between male and female patients (p = 0.460 and p = 0.725 respectively) or diabetic and non-diabetic patients (p = 0.655 and p = 0.655 respectively).
Spinal muscular atrophy (SMA), a leading genetic cause of death in childhood, is caused by deletion of the SMN1 gene, located at chromosome 5q13. The molecular pathogenesis, which results in motor neuron degeneration within the anterior horn of spinal cord, is a focus of debate among scientists. The unique nature of the duplicative 5q chromosomal region provides considerable yet challenging opportunity for disease correction as well as complication in performing molecular diagnosis and understanding the molecular pathogenesis. This article reviewed recent findings in the molecular pathogenesis of SMA as well as the research advances in the molecular diagnosis and therapeutic approaches.
Stroke causes a devastating insult to the brain resulting in severe neurological deficits because of a massive loss of different neurons and glia. In the United States, stroke is the third leading cause of death. Stroke remains a significant clinical unmet condition, with only 3% of the ischemic patient population benefiting from current treatment modalities, such as the use of thrombolytic agents, which are often limited by a narrow therapeutic time window. However, regeneration of the brain after ischemic damage is still active days and even weeks after stroke occurs, which might provide a second window for treatment. Neurorestorative processes like neurogenesis, angiogenesis and synaptic plasticity lead to functional improvement after stroke. Stem cells derived from various tissues have the potential to perform all of the aforementioned processes, thus facilitating functional recovery. Indeed, transplantation of stem cells or their derivatives in animal models of cerebral ischemia can improve function by replacing the lost neurons and glial cells and by mediating remyelination, and modulation of inflammation as confirmed by various studies worldwide. While initially stem cells seemed to work by a 'cell replacement' mechanism, recent research suggests that cell therapy works mostly by providing trophic support to the injured tissue and brain, fostering both neurogenesis and angiogenesis. Moreover, ongoing human trials have encouraged hopes for this new method of restorative therapy after stroke. This review describes up-to-date progress in cell-based therapy for the treatment of stroke. Further, as we discuss here, significant hurdles remain to be addressed before these findings can be responsibly translated to novel therapies. In particular, we need a better understanding of the mechanisms of action of stem cells after transplantation, the therapeutic time window for cell transplantation, the optimal route of cell delivery to the ischemic brain, the most suitable cell types and sources and learn how to control stem cell proliferation, survival, migration, and differentiation in the pathological environment. An integrated approach of cell-based therapy with early-phase clinical trials and continued preclinical work with focus on mechanisms of action is needed.
An understanding of the pathogenesis of glaucoma is one of the foundations in glaucoma management. A number of theories have been presented to explain glaucomatous neural degeneration. The vascular theory attempts to explain the causation of glaucoma on the basis of vasogenic factors and altered he-modynamics in the body; however, this theory remains controversial. There are proponents for and against the role played by vascular factors in the development of glaucomatous optic nerve degeneration. This review aims to analyze the various studies performed to provide evidence for and against the vascular theory of glaucoma. It also affirms the need to undertake further studies regarding the path-ogenesis of glaucoma and integrate them into our management strategies. The literature search for this systemic analysis was performed using search engines, such as PubMed, The Virtual Library of the Ministry of Health Malaysia, Google Scholar, and ClinicalKey.
Parkinson's disease (PD) is a neurodegenerative disorder defined by progressive deterioration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Dental pulp stem cells (DPSCs) have been proposed to replace the degenerated dopaminergic neurons due to its inherent neurogenic and regenerative potential. However, the effective delivery and homing of DPSCs within the lesioned brain has been one of the many obstacles faced in cell-based therapy of neurodegenerative disorders. We hypothesized that DPSCs, delivered intranasally, could circumvent these challenges. In the present study, we investigated the therapeutic efficacy of intranasally administered DPSCs in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Human deciduous DPSCs were cultured, pre-labelled with PKH 26, and intranasally delivered into PD mice following MPTP treatment. Behavioural analyses were performed to measure olfactory function and sensorimotor coordination, while tyrosine hydroxylase (TH) immunofluorescence was used to evaluate MPTP neurotoxicity in SNpc neurons. Upon intranasal delivery, degenerated TH-positive neurons were ameliorated, while deterioration in behavioural performances was significantly enhanced. Thus, the intranasal approach enriched cell delivery to the brain, optimizing its therapeutic potential through its efficacious delivery and protection against dopaminergic neuron degeneration.
Reactive oxygen species are well known for induction of oxidative stress conditions through oxidation of vital biomarkers leading to cellular death via apoptosis and other process, thereby causing devastative effects on the host organs. This effect is believed to be linked with pathological alterations seen in several neurodegenerative disease conditions. Many phytochemical compounds proved to have robust antioxidant activities that deterred cells against cytotoxic stress environment, thus protect apoptotic cell death. In view of that we studied the potential of glucomoringin-isothiocyanate (GMG-ITC) or moringin to mitigate the process that lead to neurodegeneration in various ways. Neuroprotective effect of GMG-ITC was performed on retinoic acid (RA) induced differentiated neuroblastoma cells (SHSY5Y) via cell viability assay, flow cytometry analysis and fluorescence microscopy by means of acridine orange and propidium iodide double staining, to evaluate the anti-apoptotic activity and morphology conservation ability of the compound. Additionally, neurite surface integrity and ultrastructural analysis were carried out by means of scanning and transmission electron microscopy to assess the orientation of surface and internal features of the treated neuronal cells. GMG-ITC pre-treated neuron cells showed significant resistance to H2O2-induced apoptotic cell death, revealing high level of protection by the compound. Increase of intracellular oxidative stress induced by H2O2 was mitigated by GMG-ITC. Thus, pre-treatment with the compound conferred significant protection to cytoskeleton and cytoplasmic inclusion coupled with conservation of surface morphological features and general integrity of neuronal cells. Therefore, the collective findings in the presence study indicated the potentials of GMG-ITC to protect the integrity of neuron cells against induced oxidative-stress related cytotoxic processes, the hallmark of neurodegenerative diseases.
One of the most significant hallmarks of aging is cognitive decline. D-galactose administration may impair memory and mimic the effects of natural aging. In this study, the efficiency of goat milk to protect against memory decline was tested. Fifty-two male Sprague-Dawley rats were randomly divided into four groups: (i) control group, (ii) goat milk treated group, (iii) D-galactose treated group, and (iv) goat milk plus D-galactose treated group. Subcutaneous injections of D-galactose at 120 mg/kg and oral administrations of goat milk at 1 g/kg were chosen for the study. Goat milk and D-galactose were administered concomitantly for 6 weeks, while the control group received saline. After 6 weeks, novel object recognition and T-maze tests were performed to evaluate memory of rats. Following behavioral tests, the animals were sacrificed, and right brain homogenates were analyzed for levels of lipid peroxidation, antioxidant enzymes and neurotrophic factors. The left brain hemisphere was used for histological study of prefrontal cortex and hippocampus. There was a significant memory impairment, an increase in oxidative stress and neurodegeneration and a reduction in antioxidant enzymes and neurotrophic factors levels in the brain of D-galactose treated rats compared to controls. Goat milk treatment attenuated memory impairment induced by D-galactose via suppressing oxidative stress and neuronal damage and increasing neurotrophic factors levels, thereby suggesting its potential role as a geroprotective food.
Stem cell therapy provides a ray of hope for treating neurodegenerative diseases (ND). Bone marrow mesenchymal stem cells (BM-MSC) were extensively investigated for their role in neuroregeneration. However, drawbacks like painful bone marrow extraction, less proliferation and poor CNS engraftment following systemic injections of BM-MSC prompt us to search for alternate/appropriate source of MSC for treating ND. In this context, dental pulp stem cells (DPSC) could be an alternative to BM-MSC as it possess both mesenchymal and neural characteristic features due to its origin from ectoderm, ease of isolation, higher proliferation index and better neuroprotection. A study on the migration potential of DPSC compared to BM-MSC in a neurodegenerative condition is warranted. Given the neural crest origin, we hypothesize that DPSC possess better migration towards neurodegenerative milieu as compared to BM-MSC. In this prospect, we investigated the migration potential of DPSC in an in vitro neurodegenerative condition. Towards this, transwell, Matrigel and chorioallantoic membrane (CAM) migration assays were carried-out by seeding hippocampal neurons in the lower chamber and treated with 300 μM kainic acid (KA) for 6 h to induce neurodegeneration. Subsequently, the upper chamber of transwell was loaded with DPSC/BM-MSC and their migration potential was assessed following 24 h of incubation. Our results revealed that the migration potential of DPSC/BM-MSC was comparable in non-degenerative condition. However, following injury the migration potential of DPSC towards the degenerating site was significantly higher as compared to BM-MSC. Furthermore, upon exposure of naïve DPSC/BM-MSCs to culture medium derived from neurodegenerative milieu resulted in significant upregulation of homing factors like SDF-1alpha, CXCR-4, VCAM-1, VLA-4, CD44, MMP-2 suggesting that the superior migration potential of DPSC might be due to prompt expression of homing factors in DPSC compared to BM-MSCs.
The resin/gum of Boswellia species belonging to the family of Burseraceae is a naturally occurring mixture of bioactive compounds, which was traditionally used as a folk medicine to treat conditions like chronic inflammation. Several research studies have also explored its' therapeutic potential against multiple neurodegenerative diseases such as Alzheimer's disease (AD). The main chemical constituents of this gum include boswellic acids (BAs) like 3-O-acetyl-11-keto-β boswellic acid (AKBA) that possess potent anti-inflammatory and neuroprotective properties in AD. It is also involved in inhibiting the acetylcholinesterase (AChE) activity in the cholinergic pathway and improve choline levels as well as its binding with nicotinic receptors to produce anti-inflammatory effects. Multiple shreds of evidence have demonstrated that BAs modulate key molecular targets and signalling pathways like 5-lipoxygenase/cyclooxygenase, Nrf2, NF-kB, cholinergic, amyloid-beta (Aβ), and neurofibrillary tangles formation (NFTs) that are involved in AD progression. The present review focuses on the possible mechanistic therapeutic role of BAs in modulating the 5-LOX/COX pathway in arachidonic acid metabolism, activating Nrf2 through binding of ARE, inhibiting NF-kB and AChE activity. In addition, an inhibition of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) induced neurotoxicity and neuroinflammation in AD by BAs is also discussed in this review. We have also highlighted that BAs possess beneficial effects in AD by targeting multiple molecular pathways and makes it an emerging drug candidate for treating neurodegenerative diseases.
Glaucoma is an optic neuropathy characterised by optic nerve degeneration associated with
visual field defects. It remains the world’s number one cause of irreversible blindness and
patients usually present at late stage of the disease since it is generally asymptomatic until
severe. The disease is subdivided into primary and secondary with primary open-angle
glaucoma (POAG) being the most common type. At present, lowering the intraocular pressure
(IOP) remains the only proven efficient approach in delaying the onset or preventing the
progression of the disease. Medical treatment with topical antiglaucoma agents is the
treatment of choice in open angle glaucoma. The use of antiglaucoma drugs aims to reduce
IOP by enhancing aqueous humour (AH) outflow, reducing AH production, or both. The choice
to use any available treatment option should be carefully considered in an attempt to maximise
benefits and reducing the risk of developing adverse drug reactions. This review highlights the
six classes of ocular hypotensive agents currently in use for POAG treatment including
prostaglandin analogues; -adrenergic receptor blockers; -2 adrenergic receptor stimulants;
carbonic anhydrase inhibitors; muscarinic receptor stimulants; rho kinase inhibitors with
regards to their mechanism/s of action and potential adverse drug reactions, and
antiglaucoma fixed drug combinations.
Alzheimer's disease (AD) as a neurodegenerative brain disorder is the most common cause of dementia. To date, there is no causative treatment for AD and there are few preventive treatments either. The sphingosine-1-phosphate receptor modulator FTY720 (fingolimod) prevents lymphocytes from contributing to an autoimmune reaction and has been approved for multiple sclerosis treatment. In concert with other studies showing the anti-inflammatory and protective effect of FTY720 in some neurodegenerative disorders like ischemia, we have recently shown that FTY720 chronic administration prevents from impairment of spatial learning and memory in AD rats. Here FTY720 was examined on AD rats in comparison to the only clinically approved NMDA receptor antagonist, Memantine. Passive avoidance task showed significant memory restoration in AD animals received FTY720 comparable to Memantine. Upon gene profiling by QuantiGene Plex, this behavioral outcomes was concurrent with considerable alterations in some genes transcripts like that of mitogen activated protein kinases (MAPKs) and some inflammatory markers that may particularly account for the detected decline in hippocampal neural damage or memory impairment associated with AD. From a therapeutic standpoint, our findings conclude that FTY720 may suggest new opportunities for AD management probably based on several modulatory effects on genes involved in cell death or survival.
Matched MeSH terms: Nerve Degeneration/chemically induced; Nerve Degeneration/prevention & control