Recent Progresses in Brain Gene Therapy

Afsoun Seddighi, Amir Nikouei, Amir Saied Seddighi, Mohammad Asadpour, Noushin Masoudian, Afshin Samaie

International Clinical Neuroscience Journal, Vol. 3 No. 4 (2016), 7 February 2017 , Page 177-181

Gene therapy consists of the introduction of genetic material into cells for a therapeutic purpose. The understanding of the basics of the molecular and cellular mechanisms in disease treatments has resulted in the development of high-tech gene transfer materials with improved therapeutic efficacy. Based on the results of more than 2000 clinical trials to date, gene therapy is going to be included in standard treatment approaches in some specific diseases. Also, gene therapy has been highly improved in central and peripheral nervous system diseases. This review tried to focus on techniques and approaches in brain tumors and nervous system’s gene therapy strategies and will discuss about associated problems and potential future in management of inherited or acquired neurological disorders.

Pre-Differentiated Embryonic Stem Cell versus Olfactory Ensheathing Cell for Spinal Cord Regeneration after Compressive Injury in Rat

Mohammad Salehi, Saeed Oraee-Yazdani, Alireza Zali, Masoud Soleimani

International Clinical Neuroscience Journal, Vol. 3 No. 4 (2016), 7 February 2017 , Page 182-192

Background: Transplantation approaches are interventions currently available to apply to the devastating problem of spinal cord injury (SCI). Olfactory ensheathing cell (OEC) and embryonic stem cell (ESC) are considered to be promising therapeutic strategies. In this study, we compared the potential use of OECs and neurally pre-differentiated ESCs in contusion spinal cord.

Methods: OECs were harvested from olfactory bulb of rats and labeled with Hoescht 33342. ESCs were generated by using feeder free GFP positive CGR8 mouse ESCs and neurally pre-differentiation was induced by retinoic acid (RA) and characterized by different antibodies. SCI was induced by fogarty catheter at T8-T9 level in adult rats. Transplantations were performed 9 days after the injury. Rats were randomly divided into 3 main groups (neurally pre-differentiated ESC, OEC and media as control group). The recovery of gross motor function was evaluated using Basso-Beattie-Bresnahan (BBB) locomotor rating scale on the ninth day post injury and once per week thereafter for 4 weeks after cell transplantation. At 28 days after transplantation, histological assessment including transplanted cell detection in tissue, tissue sparing and myelinated axons was performed.

Results: Following transplantation, a significant recovery of hindlimb function according to BBB scale was observed in rats in the transplanted groups compared to control and sham groups (p<0.05). There was no significant difference between transplanted groups four weeks after transplantation. OEC and ESC were found in the tissue after transplantation. In OEC group, many of OECs were detected around and within the cystic cavity that number of these cells was significantly higher in comparison with number of cells in ESC group (p< 0.001).

In the site of injury, several cavities were produced that disrupted portions of the gray and white matters. The extent of tissue damage was more severe in the sham and control groups than the other groups. Significantly more spinal tissue was spared in OEC and ESC groups (P < 0.001). No significant difference in percentage of spared tissue was found between sham and control groups or transplanted groups. The percentage of myelinated area was greater in OEC group than in three other groups (p< 0.05) (Figure 5, A). Although the percentage of myelinated area was more in ESC group in comparison with non-treated groups, but this difference was not significant.

Conclusion: It seems that using of combination of a myelinating cells like OEC or schwann cell and source of cells to replace dead cells like Mesenchymal or embryonic stem cells, better results can be obtained due to probable synergic effects of these cells.

Effects of 660nm Low-Level Laser Therapy on P2X3 Expression of Lumbar DRG of Adult Male Rats with Neuropathic Pain

Mahdieh Kerdari, Ghazal Hamid Behnam, Mona Farhadi, Masumeh Masoumipoor, Sajad Hassanzadeh, Maryam Soleimani, Alireza Kazemian, Mahsa Jalilpourmoghadam, Seyed Behnamedin Jameie

International Clinical Neuroscience Journal, Vol. 3 No. 4 (2016), 7 February 2017 , Page 193-200

Background: Neuropathic Pain (NP) is a serious suffering medical condition that frequently leads to disability and life style changes. Although the exact mechanisms of NP are still unknown, recently the role of reactive oxygen species (ROS) reported as an important factor for NP. Apoptosis, increase of ATP production and reduction of antioxidants are also the other factors influencing in NP. There are certain therapeutic procedures for NP among them using laser therapy newly received more attention. In the present research we studied the molecular effects of Low Level Laser Therapy (LLLT) on a rat model of NP.

Methods: Thirty adult male Wistar rats (200-250 g) that randomly divided into three groups including chronic constriction injury (CCI), CCI+LLLT and control were used in this study. CCI technique was used to induce NP. Laser therapy was done by using laser beam of 660 for 14 days following CCI. After that, expression of P2X3 of the DRG, Bax and Bcl2 in lumbar spinal segments measured by Western Blotting. Level of glutathione (GSH) was also measured in lumbar spinal cord segments by Continuous Spectrophotometric Rate Determination method. For behavioral study the mechanical and thermal hyperalgesia were evaluated in days 7 and 14 after CCI.

Results: LLLT for two weeks increased expression of Bcl2 and GSH, whereas decreased Bax and P2X3 expression significantly. Comparing the results of behavioral study showed significant differences in the mechanical and thermal threshold showed between CCI and CCI+ LLLT groups.

Conclusion: Based on our findings, the therapeutic effects of LLLT for NP act throughout cellular and molecular mechanisms which improve mitochondrial function that in turn improve cell function and prevent apoptosis. 

Differentiation Induction Effect of Mir-429 Over-Expression in U251 Glioma Cell Line

Fatemeh Gheidari, Ehsan Arefian, Fatemeh Jamshidi-Adeghani, Masoud Soleimani

International Clinical Neuroscience Journal, Vol. 3 No. 4 (2016), 7 February 2017 , Page 201-205

The purpose of this research was to investigate the effect of mir-429 ectopic over-expression on U251 glioblastoma cell line. It has been shown that mir-429 could target BMK1 and reduce glioma cells invasion. We cultured U251-mir-429 cells and observed changes in their morphology for 14 days. They seemed to become wider with expanded cytoplasm and go on differentiation. Neuronal (NEFM, NSE and neurogenin) and oligodendrocyte (MBP, OLIG2 and NKX2-2) gene markers expression level was examined with real-time PCR. NSE, neurogenin, MBP, OLIG2 and NKX2-2 were significantly over-expressed, giving an evidence of cellular differentiation in glioma cells.

Ceftriaxone Decreases MPTP-induced Behavioral Disturbances in Animal Model of Parkinson’s disease

Mohammad Amiri, Reza Taherian, Hossein Nazari, Mahdi Taherian

International Clinical Neuroscience Journal, Vol. 3 No. 4 (2016), 7 February 2017 , Page 206-213

Background and purpose: Progressive degeneration of dopaminergic neurons in the midbrain is the main mechanism of Parkinson’s disease (PD). Recent studies have shown ceftriaxone, a β-lactam antibiotic, to be a neuroprotective in various neurodegenerative disorders. Hence, the present study aimed to investigate the effect of ceftriaxone on behavioral disturbances of PD in an animal model.

Methods: Fifty-six healthy male Wistar rats were selected for this study. They were divided into seven groups according to receiving saline or ceftriaxone, receiving a low or high dose of ceftriaxone and receiving ceftriaxone for short or long periods. Apomorphine-induced rotational test, elevated body swing test and rotarod test were done to examine behavioral performances.

Results: Ceftriaxone can effectively diminish behavioral disturbances induced by MPTP in all behavioral tests. Long administration of ceftriaxone was more effective than short administration in lowering behavioral disturbances. High dose of ceftriaxone was more effective than low dose in initial trials of each behavioral test; however, no difference was observed between them in the last trial.

Conclusion: Results of the current study suggest that ceftriaxone have neuroprotective effects in PD. To obtain a sufficient neuroprotective effect for lowering behavioral disturbances of PD and also preventing side effects of ceftriaxone, long administration of low dose of ceftriaxone seems the best option.

The Effect of Greater Occipital Nerve Block on Chronic Migraine

Mahdi Safiabadi, Sirous Tayebi, Mahdi Heshmatifar

International Clinical Neuroscience Journal, Vol. 3 No. 4 (2016), 7 February 2017 , Page 214-218

Background: Greater occipital never block has been shown to be an effective treatment in patients with cluster or tension type headache but there are very few studies investigating its effect in patients with chronic migraine. This study was to determine the effectiveness of greater occipital never block on headache in patients with chronic migraine. We designed an interventional before-after study for patients suffered from chronic migraine.

Methods: Patients were participated in this study according to inclusion and exclusion criteria. Frequency, severity and duration of headaches were recorded by patients 2 weeks before injection and then during 6 weeks after injection. We compared data recorded before injection to data from each two-week after injections to determine the effectiveness of greater occipital never block in improvement of headaches in patients with chronic migraine.

Results: Fourteen patients (mean age=34.21±2.75) were included in the study. Number of attacks was significantly decreased during 6 weeks follow up (p<0.05). Mean headache severity was significantly decreased during first and second two-week follow up by 3.04 and 2.39 points, respectively. Duration of headaches was not significantly reduced during follow up.

Conclusion: In conclusion, Greater occipital nerve block can improve the status of headache in patients with chronic migraine by decreasing the severity and frequency of headaches. However, it may not be effective in shortening the duration of headaches.

CLIPPERS: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive To Steroids

Farhad Assarzadegan, Omid Hesami, Behnam Safarpour Lima, Anahita Zoghi, Ehsan Sakhaee

International Clinical Neuroscience Journal, Vol. 3 No. 4 (2016), 7 February 2017 , Page 219-223

A novel type of brainstem-predominant encephalomyelitis was first described as chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in 2010 by Pittocket al and then few additional patients were reported. Here we report a 50-year-old Iranian male who presented with a number of clinical features described as typical for CLIPPERS. The association of typical clinical presentation and typical MR imaging could be sufficient for a reliable diagnosis of CLIPPERS.

Simple Bone Cyst in the Body of the Lumbar Vertebra

Mohamad Ali Fazeli, Zahra Janamiri, Amirsaeed Seddighi

International Clinical Neuroscience Journal, Vol. 3 No. 4 (2016), 7 February 2017 , Page 224-226

Simple bone cysts are usual, benign, fluid-filled, cystic lesions that often occur in the metaphysis of the long bones and are rarely detected in vertebrae. A case of a simple bone cyst in the body of the fifth lumbar vertebra in a 28-year-old woman with complaint of intermittent low back pain is described. According to the radiologic findings, the lesion was detected as a simple bone cyst, and the diagnosis was determined by imaging.