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Fulltext Stem cell therapy as a potential treatment for glaucoma

Kamal, M., Amini, F., Ramasamy, TS

JUMMEC, 2016;19(1):23-32.
MyJurnal

Glaucoma is a common eye disease that can cause irreversible damage if left undiagnosed and untreated. It is one of the most common neurodegenerative diseases causing blindness. Pre-clinical studies have been carried out on animal models of glaucoma for stem cell therapy. We carried out a systematic review to determine whether stem cell therapy had the potential to treat glaucoma. Nine studies were selected based on the predetermined inclusion and exclusion criteria. Of these nine studies, eight focused on neuroprotection conferred by stem cells, and the remaining one on neuroregeneration. Results from these studies showed that there was a potential in stem cell based therapy in treating glaucoma, especially regarding neuroprotection via neurotrophic factors. The studies revealed that a brain-derived neurotrophic factor expressed by stem cells promoted the survival of retinal ganglion cells in murine glaucoma models. The transplanted cells survived without any side effects. While these studies proved that stem cells provided neuroprotection in glaucoma, improvement of vision could not be determined. Clinical studies would be required to determine whether the protection of RGC correlated with improvement in visual function. Furthermore, these murine studies could not be translated into clinical therapy due to the heterogeneity of the experimental methods and the
use of different cell lines. In conclusion, the use of stem cells in the clinical therapy of glaucoma will be an important step in the future as it will transform present-day treatment with the hope of restoring sight to patients with glaucoma.

Matched MeSH terms: Nerve Regeneration
Fulltext Melatonin promotes Schwann cell dedifferentiation and proliferation through the Ras/Raf/ERK and MAPK pathways, and glial cell-derived neurotrophic factor expression

Tiong YL, Ng KY, Koh RY, Ponnudurai G, Chye SM

Exp Ther Med, 2020 Nov;20(5):16.
PMID: 32934681 DOI: 10.3892/etm.2020.9143

Upon peripheral nerve injury (PNI), continuous proliferation of Schwann cells is critical for axon regeneration and tubular reconstruction for nerve regeneration. Melatonin is a hormone that is able to induce proliferation in various cell types. In the present study, the effects of melatonin on promoting Schwann cell proliferation and the molecular mechanism involved were investigated. The present results showed that melatonin enhanced the melatonin receptors (MT1 and MT2) expression in Schwann cells. Melatonin induced Schwann cell dedifferentiation into progenitor-like Schwann cells, as observed by immunofluorescence staining, which showed Sox2 marker expression. In addition, melatonin enhanced Schwann cell proliferation, mediated by the upregulation of glial cell-derived neurotropic factor (GNDF) and protein kinase C (PKC). Furthermore, the Ras/Raf/ERK and MAPK signaling pathways were also involved in Schwann cell dedifferentiation and proliferation. In conclusion, melatonin induced Schwann cell dedifferentiation and proliferation via the Ras/Raf/ERK, MAPK and GDNF/PKC pathways. The present results suggested that melatonin could be used to enhance the recovery of PNI.

Matched MeSH terms: Nerve Regeneration
Fulltext The Changes in Rats with Sciatic Nerve Crush Injury Supplemented with Evening Primrose Oil: Behavioural, Morphologic, and Morphometric Analysis

Ramli D, Aziz I, Mohamad M, Abdulahi D, Sanusi J

Evid Based Complement Alternat Med, 2017;2017:3476407.
PMID: 28620418 DOI: 10.1155/2017/3476407

Nerve crush injuries are commonly used models for axonotmesis to examine peripheral nerve regeneration. As evening primrose oil (EPO) is rich in omega-6 essential fatty acid component and gamma-linolenic acid, studies have shown the potential role of EPO in myelination. Seventy-two healthy adult Sprague-Dawley rats were classified into three groups: normal group, control group, and experimental group. The result indicates that there was significant difference in toe-spreading reflex between the normal and the control groups (1.9 ± 0.031, p < 0.05) and the normal and the EPO groups (0.4 ± 0.031, p < 0.05) and significant difference between EPO and the control groups (1.5 ± 0.031, p < 0.05). Regeneration of axons and myelin in nerve fibre in the EPO-treated group developed better and faster than in the control group. In the control group, the shape of the axon was irregular with a thinner myelin sheath. In the experimental group, the shape of the axons, the thickness of the myelin sheath, and the diameter of the axons were almost the same as in the normal group. In conclusion, EPO supplementation may be beneficial as a therapeutic option for disturbances of nerve interaction.

Matched MeSH terms: Nerve Regeneration
Fulltext Recent Updates in Neuroprotective and Neuroregenerative Potential of Centella asiatica

Lokanathan Y, Omar N, Ahmad Puzi NN, Saim A, Hj Idrus R

Malays J Med Sci, 2016 Jan;23(1):4-14.
PMID: 27540320 MyJurnal

Centella asiatica, locally well known in Malaysia as pegaga, is a traditional herb that has been used widely in Ayurvedic medicine, traditional Chinese medicine, and in the traditional medicine of other Southeast Asian countries including Malaysia. Although consumption of the plant is indicated for various illnesses, its potential neuroprotective properties have been well studied and documented. In addition to past studies, recent studies also discovered and/or reconfirmed that C. asiatica acts as an antioxidant, reducing the effect of oxidative stress in vitro and in vivo. At the in vitro level, C. asiatica promotes dendrite arborisation and elongation, and also protects the neurons from apoptosis. In vivo studies have shown that the whole extract and also individual compounds of C. asiatica have a protective effect against various neurological diseases. Most of the in vivo studies on neuroprotective effects have focused on Alzheimer's disease, Parkinson's disease, learning and memory enhancement, neurotoxicity and other mental illnesses such as depression and anxiety, and epilepsy. Recent studies have embarked on finding the molecular mechanism of neuroprotection by C. asiatica extract. However, the capability of C. asiatica in enhancing neuroregeneration has not been studied much and is limited to the regeneration of crushed sciatic nerves and protection from neuronal injury in hypoxia conditions. More studies are still needed to identify the compounds and the mechanism of action of C. asiatica that are particularly involved in neuroprotection and neuroregeneration. Furthermore, the extraction method, biochemical profile and dosage information of the C. asiatica extract need to be standardised to enhance the economic value of this traditional herb and to accelerate the entry of C. asiatica extracts into modern medicine.

Matched MeSH terms: Nerve Regeneration
Immediate selective laryngeal reinnervation in vagal paraganglioma patients

Mat Baki M, Clarke P, Birchall MA

J Laryngol Otol, 2018 Sep;132(9):846-851.
PMID: 30180919 DOI: 10.1017/S0022215118000476

OBJECTIVE: This prospective case series aimed to present the outcomes of immediate selective laryngeal reinnervation.
METHODS: Two middle-aged women with vagal paraganglioma undergoing an excision operation underwent immediate selective laryngeal reinnervation using the phrenic nerve and ansa cervicalis as the donor nerve. Multidimensional outcome measures were employed pre-operatively, and at 1, 6 and 12 months post-operatively.
RESULTS: The voice handicap index-10 score improved from 23 (patient 1) and 18 (patient 2) at 1 month post-operation, to 5 (patient 1) and 1 (patient 2) at 12 months. The Eating Assessment Tool 10 score improved from 20 (patient 1) and 24 (patient 2) at 1 month post-operation, to 3 (patient 1) and 1 (patient 2) at 12 months. There was slight vocal fold abduction observed in patient one and no obvious abduction in patient two.
CONCLUSION: Selective reinnervation is safe to perform following vagal paraganglioma excision conducted on the same side. Voice and swallowing improvements were demonstrated, but no significant vocal fold abduction was achieved.

Matched MeSH terms: Nerve Regeneration/physiology
Role of melatonin in neurodegenerative diseases

Srinivasan V, Pandi-Perumal SR, Maestroni GJ, Esquifino AI, Hardeland R, Cardinali DP

Neurotox Res, 2005;7(4):293-318.
PMID: 16179266

The pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases, e.g., Alzheimer's disease. Melatonin has been shown to be effective in arresting neurodegenerative phenomena seen in experimental models of Alzheimer's disease, Parkinsonism and ischemic stroke. Melatonin preserves mitochondrial homeostasis, reduces free radical generation, e.g., by enhancing mitochondrial glutathione levels, and safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. Therapeutic trials with melatonin have been effective in slowing the progression of Alzheimer's disease but not of Parkinson's disease. Melatonin's efficacy in combating free radical damage in the brain suggests that it may be a valuable therapeutic agent in the treatment of cerebral edema after traumatic brain injury.

Matched MeSH terms: Nerve Regeneration/drug effects
Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration

Wong KH, Kanagasabapathy G, Naidu M, David P, Sabaratnam V

Chin J Integr Med, 2016 Oct;22(10):759-67.
PMID: 25159861 DOI: 10.1007/s11655-014-1624-2

OBJECTIVE: To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats.
METHODS: Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method.
RESULTS: Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05).
CONCLUSION: H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Matched MeSH terms: Nerve Regeneration/physiology*
Photobiomodulation After Neurotization (Oberlin Procedure) in Brachial Plexus Injury: A Randomized Control Trial

Foo YH, Tunku Ahmad Yahaya TS, Chung TY, Silvanathan JP

Photobiomodul Photomed Laser Surg, 2020 Apr;38(4):215-221.
PMID: 32301668 DOI: 10.1089/photob.2019.4757

Objective:
To investigate effect of photobiomodulation (PBM) on nerve regeneration after neurotization with the Oberlin Procedure (ulnar fascicle to motor branch to biceps) to restore elbow flexion in patients with brachial plexus injury.
Materials and methods:
This prospective randomized controlled trial was conducted with 14 patients with high brachial plexus injury who underwent neurotization with the Oberlin Procedure to restore elbow flexion. The patients were randomly allocated to two groups of equal numbers: control group and PBM group. In this study, the PBM used has a wavelength of 808 nm, 50 mW power, continuous mode emission, 4 J/cm2 dosimetry, administered daily for 10 consecutive days, with an interval of 2 days (weekends). The outcome of surgery was assessed after 1, 2, 3, and 6 months. The nonparametric Mann-Whitney U-test and chi-square test were utilized to compare the results between both groups.
Results:
After 3 months postoperatively, more patients in the PBM group had demonstrated signs of reinnervation and the mean muscle power was significantly higher in the PBM group. No adverse effects resulted from the administration of PBM.
Conclusions:
PBM is a treatment modality that can improve nerve regeneration after neurotization with the Oberlin Procedure.

Matched MeSH terms: Nerve Regeneration
Adult stem cells: a clinical update

Totey S, Totey S, Pal R, Pal R

J Stem Cells, 2009;4(2):105-21.
PMID: 20232596

There has been unprecedented interest in stem cell research mainly because of their true potential and hope that they offer to the patients as a cell therapy with the prospect to treat hitherto incurable diseases. Despite the worldwide interest and efforts that have been put in this research, major fundamental issues are still unresolved. Adult stem cells such as hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) are already under clinical applications and there are several examples of plasticity and self-renewal where adult stem cells or their precursor cells can be re-programmed by extra cellular cues or internal cues to alter their character in a way that could have important application for cell therapy and regenerative medicine. From a clinical perspective, no other area of stem cell biology has been applied as successfully as has transplantation of bone marrow stem cells and cord blood stem cells for the treatment of hematological diseases. In the last few years, research in stem cell biology has expanded staggeringly, engendering new perspectives concerning the identity, origin, and full therapeutic potential of tissue-specific stem cells. This review will focus on the use of adult stem cells, its biology in the context of cell plasticity and their therapeutic potential for repair of different tissues and organs.

Matched MeSH terms: Nerve Regeneration