Transition nuclear protein 1 as a novel biomarker in patients with fertilization failure / 대한생식의학회지

Objective@#Although intracytoplasmic sperm injection (ICSI) is a way to deal with in vitro fertilization failure, 3% of couples still experience repeated fertilization failure after attempted ICSI, despite having sperm within normal parameters. These patients are a challenging group whose sperm cannot fertilize the egg during ICSI. Unfortunately, no test can predict the risk of fertilization failure. Phospholipase C zeta (PLCζ) and transition nuclear proteins (TNPs) are essential factors for chromatin packaging during sperm maturation. This study aimed to assess PLCζ1 and TNP1 expression in the sperm of patients with fertilization failure and the correlations among the DNA fragmentation index, PLCζ1 and TNP1 gene and protein expression, and the risk of fertilization failure. @*Methods@#In this study, 12 infertile couples with low fertilization rates (<25%) and complete failure of fertilization in their prior ICSI cycles despite normal sperm parameters were chosen as the case group. Fifteen individuals who underwent ICSI for the first time served as the control group. After sperm analysis and DNA fragmentation assays, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to compare the gene and protein expression of PLCζ and TNP1 in both groups. @*Results@#DNA fragmentation was significantly higher in the fertilization failure group. The qRT-PCR and Western blot results demonstrated significantly lower PLCζ and TNP1 gene and protein expression in these patients than in controls. @*Conclusion@#The present study showed that fertilization failure in normozoospermic men was probably due to deficient DNA packaging and expression of TNP1.

Evaluation of polyglycolic acid as an animal-free biomaterial for three-dimensional culture of human endometrial cells / 대한생식의학회지

Objective@#Animal-free scaffolds have emerged as a potential foundation for consistent, chemically defined, and low-cost materials. Because of its good potential for high biocompatibility with reproductive tissues and well-characterized scaffold design, we investigated whether polyglycolic acid (PGA) could be used as an animal-free scaffold instead of natural fibrin-agarose, which has been used successfully for three-dimensional human endometrial cell culture. @*Methods@#Isolated primary endometrial cells was cultured on fibrin-agarose and PGA polymers and evaluated various design parameters, such as scaffold porosity and mean fiber diameter. Cytotoxicity, scanning electron microscopy (SEM), and immunostaining experiments were conducted to examine cell activity on fabricated scaffolds. @*Results@#The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and SEM results showed that endometrial cells grew and proliferated on both scaffolds. Immunostaining showed cytokeratin and vimentin expression in seeded cells after 7 days of culture. On both scaffolds, an epithelial arrangement of cultured cells was found on the top layer and stromal arrangement matrix on the bottom layer of the scaffolds. Therefore, fibrin-agarose and PGA scaffolds successfully mimicked the human endometrium in a way suitable for in vitro analysis. @*Conclusion@#Both fibrin-agarose and PGA scaffolds could be used to simulate endometrial structures. However, because of environmental and ethical concerns and the low cost of synthetic polymers, we recommend using PGA as a synthetic polymer for scaffolding in research instead of natural biomaterials.

Frequency, shape, and estimated volume of intracranial physiologic calcification in different age groups investigated by brain computed tomography scan: a retrospective study / 대한해부학회지

Intracranial calcification is referred to calcification of parenchyma and vascular structures in brain which can be physiologic or pathologic. This study was conducted with the purpose of investigating the frequency, location, pattern, dimensions and estimated volume of intracranial physiologic calcification (IPC) by computer tomography in different age groups. In this cross-sectional retrospective study, brain computed tomography scans of 216 patients were analyzed in 9 age groups each containing 24 patients from 2 to 89 years old. Data were analyzed by SPSS software using one way analysis of variance (ANOVA, post hoc Tukey), chi square, and linear regression tests (P≤0.05 was considered significant). Rate of calcification in different areas were as follows: pineal gland (75.0%), habenula (36.4%), pineohabenula (15.0%), right lateral ventricle choroid plexus (RCP) (67.7%), left lateral ventricle choroid plexus (LCP) (62.7%), falx cerebri (26.8%), petroclinoid ligament (13.2%), tentorium cerebelli (6.8%), third ventricle choroid plexus (0.9%), fourth ventricle choroid plexus (2.7%), basal ganglia (0.9%). A significant correlation exists between the presence of calcification in pineal, habenula, RCP, and LCP (P≤0.001). Nodular shape of calcification was dominant (47.9%). Estimated volume of pineal calcification showed increased levels in group 8 (70–79 years old) compared to group 2 (10–19 years old) (P≤0.05). Since the accurate description of radiologic appearance of IPCs (location, shape, and size) accompanied with age and clinical manifestation is of great importance in diagnosis and distinguishing from pathologic calcification—for example in patients with melatonin dysregulation or schizophrenic patients—this study was required.

Health concerns regarding the effect of the COVID-19 pandemic on male fertility / 대한생식의학회지

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus found in China in 2019. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), has been found to be closely related to the cells that secrete angiotensin-converting enzyme 2 (ACE2). ACE2 is involved in the renin-angiotensin system and is widely secreted in several tissues, including the testis, which has raised concerns because organs with high expression of the ACE2 receptor are susceptible to infection. Analyses have shown that in testicular cells, such as spermatogonia, seminiferous duct cells, Sertoli cells, and Leydig cells, there is a high expression level of ACE2. Therefore, SARS-CoV-2 may damage male reproductive tissues and cause infertility. Since male infertility is an important problem, scientists are evaluating whether COVID-19 may influence male infertility through the ACE2 receptor.

Health concerns regarding the effect of the COVID-19 pandemic on male fertility / 대한생식의학회지

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus found in China in 2019. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), has been found to be closely related to the cells that secrete angiotensin-converting enzyme 2 (ACE2). ACE2 is involved in the renin-angiotensin system and is widely secreted in several tissues, including the testis, which has raised concerns because organs with high expression of the ACE2 receptor are susceptible to infection. Analyses have shown that in testicular cells, such as spermatogonia, seminiferous duct cells, Sertoli cells, and Leydig cells, there is a high expression level of ACE2. Therefore, SARS-CoV-2 may damage male reproductive tissues and cause infertility. Since male infertility is an important problem, scientists are evaluating whether COVID-19 may influence male infertility through the ACE2 receptor.

Impaired memory and evidence of histopathology in CA1 pyramidal neurons through Injection of Abeta1-42 peptides into the frontal cortices of rat

Introduction: Alzheimer's disease [AD] is one of the most common neurodegenerative disorders, which has much benefited from animal models to find the basics of its pathophysiology. In our previous work [Haghani, Shabani, Javan, Motamedi, and Janahmadi, 2012], a non-transgenic rat model of AD was used in electrophysiological studies. However, we did not investigate the histological aspects in the mentioned study

Methods: An AD model was developed through bilateral injection of amyloid-beta peptides [Abeta] into the frontal cortices. Behavioral and histological methods were used to assess alterations in the memory and [ultra]structures. Furthermore, melatonin has been administered to assess its efficacy on this AD model

Results: Passive avoidance showed a progressive decline in the memory following Abeta injection. Furthermore, Nissl staining showed that Abeta neurotoxicity caused shrinkage of the CA1 pyramidal neurons. Neurodegeneration was clearly evident from Fluoro-jade labeled neurons in Abeta treated rats. Moreover, higher NF-kappaB immunoreactive CA1 pyramidal neurons were remarkably observed in Abeta treated rats. Ultrastructural analysis using electron microscopy also showed the evidence of subcellular abnormalities. Melatonin treatment in this model of AD prevented Abeta- induced increased NF-kappaB from immunoreaction and neurodegeneration

Discussion: This study suggests that injection of Abeta into the frontal cortices results in the memory decline and histochemical disturbances in CA1 pyramidal neurons. Furthermore, melatonin can prevent several histological changes induced by Abeta

Transforming growth factor -alpha improves memory impairment and neurogenesis following ischemia reperfusion

Stroke is most important cause of death and disability in adults. The hippocampal CA1 and sub-ventricular zone neurons are vulnerable to ischemia that can impair memory and learning functions. Although neurogenesis normally occurs in the dentate gyrus [DG] of the hippocampus and sub-ventricular zone [SVZ] following brain damage, this response is unable to compensate for severely damaged areas. This study aims to assess both neurogenesis and the neuroprotective effects of transforming growth factor-alpha [TGF-alpha] on the hippocampus and SVZ following ischemia-reperfusion. In this experimental study, a total of 48 male Wistar rats were divided into the following groups: surgical [n=12], phosphate buffered saline [PBS] treated vehicle shams [n=12], ischemia [n=12] and treatment [n=12] groups. Ischemia was induced by common carotid occlusion for 30 minutes followed by reperfusion, and TGF-alpha was then injected into the right lateral ventricle. Spatial memory was assessed using Morris water maze [MWM]. Nestin and Bcl-2 family protein expressions were studied by immunohistochemistry [IHC] and Western blot methods, respectively. Finally, data were analyzed using Statistical Package for the Social Sciences [SPSS, SPSS Inc., Chicago, USA] version 16 and one-way analysis of variance [ANOVA]. TGF-alpha injection significantly increased nestin expression in both the hippocampal DG and SVZ areas. TGF-alpha treatment caused a significant decrease in Bax expression and an increase in Bcl-2 anti-apoptotic protein expression in the hippocampus. Our results showed a significant increase in the number of pyramidal neurons. Memory also improved significantly following TGF-alpha treatment. Our findings proved that TGF-alpha reduced ischemic injury and played a neuroprotective role in the pathogenesis of ischemic injury

Toll-like receptors expression in follicular cells of patients with poor ovarian response

Background: Poor ovarian response [POR] to gonadotropin stimulation has led to a significant decline in success rate of fertility treatment. The immune system may play an important role in pathophysiology of POR by dysfunctions of cytokines and the growth factor network, and the presence of ovarian auto-antibodies. The aim of this study is to investigate the expression of toll-like receptors [TLR] 1, 2, 4, 5, 6 and cyclooxygenase [COX] 2 genes in follicular cells and concentration of interleukin [IL]-6, IL-8 and macrophage migration inhibitory factor [MIF], as major parts of innate immunity, in follicular fluid [FF] obtained from POR women in comparison with normal women

Materials and Methods: In this case-control study, 20 infertile POR patients and 20 normal women took part in this study and underwent controlled ovarian stimulation. The FF was obtained from the largest follicle [>18 mm]. The FF was centrifuged and cellular pellet was then used for evaluation of expression of TLRs and COX2 genes by real-time PCR. FF was used for quantitative analysis for IL-6, IL-8 and MIF by enzyme-linked immunosorbent assay [ELISA]

Results: TLR1, 2, 4, 5, 6 and COX2 gene expression were significantly higher in POR [p<0.05]. Concentration of IL-6, IL-8 and MIF proteins was significantly increased in POR compared with normal women [p<0.05]

Conclusion: These findings support the hypothesis that the immune system may be involved in pathophysiology of POR through TLRs

Effects of Coenzyme Q10 on the ratio of TH1/TH2 in experimental autoimmune encephalomyelitis model of multiple sclerosis in C57BL/6

Multiple sclerosis [MS] is known as a progressive central nervous system inflammatory disease. Certain factors, such as interleukins, inflammatory cells, and oxidative stress are supposed to involve in MS etiology. Because of the important role of oxidative stress, antioxidant therapy for MS has received more attention. Although coenzyme Q10 [CoQ10] acts as an antioxidant, there is a lack of enough research on its effects on MS. Therefore, the present research was designed. C57BL/6 female adult mice [n = 30] were used in this study. The animals were randomly divided into trial and control groups. To induce MS, routine procedure for experimental autoimmune encephalomyelitis [EAE] was used, and scoring was performed based on clinical signs. By detecting score one, CoQ10 administration was started [10 mg/kg/three weeks]. By using ELISA and real-time PCR, the brain levels of TNF-cc, IL-10, IL-4, and IL-12 were studied. Statistical tests were used to analyze the data and the P value less than 0.05 was considered to be significant. Clinical symptoms in EAE animals were significantly decreased [P<0.05] as compared to control ones. In addition, the level of the TNF-oc was significantly decreased following CoQ10 administration versus IL-10. The ratio of TH1/TH2 interleukins in treated animals was significantly less than that in non-treated animals [P<0.01]. Our findings showed that CoQ10 is capable of suppressing the inflammatory pathway of MS

Effect of combination therapy using hypothermia and granulocyte colony-stimulating factor in a rat transient middle cerebral artery occlusion model

Stroke is the third leading cause of death. Hypothermia has been recognized as an effective method in reducing brain injury. In this study, we assessed the effects of granulocyte colony-stimulating factor [G-CSF] as a neuroprotective agent and mild hypothermia on mortality, behavioral function, infarct volume, and brain edema in Wistar rats. Forty male rats were used in five groups [eight rats in each group]: control, hypothermy, G-CSF, combination hypothermy + CSF, and sham. Rats were anesthetized by injection of chloral hydrate [400 mg/kg] intraperitoneally. Transient cerebral ischemia was induced by 60-min intraluminal occlusion of left middle cerebral artery. Hypothermia, initiated at the time of reperfusion and G-CSF was started one hour after reperfusion at a dose of 15 mg/kg subcutaneously. The motor behavior was measured using Garcia's index and animals were assigned for the assessments of infarction, brain swelling, and mortality rate. The mortality was 38.46% [control group] and reduced in other groups. Neurological deficit score of control group [40.31 +/- 1.56] was significantly lower than in treatment groups. The total cerebral infarct volume of treatment group was significantly lower than control group [43.96 +/- 44.05 mm[3]]. Treatment with hypothermy plus G-CSF [2.69 + 0.24%] could significantly reduce brain swelling volume than other treatment groups. Our major finding is that mild hypothermic treatment plus G-CSF significantly reduced mortality rate and edema and improved neurological function. The results suggest that the combination of hypothermia and G-CSF is more effectively than other treatment groups being used alone

Coenzyme Q10 protects hippocampal neurons against ischemia/ reperfusion injury via modulation of Bax/Bcl-2 expression

Preliminary studies have confirmed reduction in cell death following treatment with antioxidants. According to this finding we study the relationship between consumption of CoQ10 and expression of Bax and Bcl2 in hippocampus following ischemia/reperfusion as proteins involved in cell programmed death or apoptosis. We studied the protective role of CoQ 10 against ischemia-reperfusion. Experimental design includes four groups: intact, ischemic control, sham control and treatment group with CoQ10. The mice were pre-treated with CoQ10 for a week, then ischemia was induced by common carotid artery ligation and following the reduction in inflammation [a week] the mice was treated with CoQ10. Nissl staining was applied for counting the necrotic cells of hippocampus and the western blot was performed to measure the Bax and Bcl2 expression. Cell death was significantly lower when mice were treated with CoQ10. Bax expression was significantly high in the ischemic group but low in the treatment group, and the bcl2 expression was lower in the ischemic group than the treatment and the vehicle groups. Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQI0 intake significantly reduced cell death and prevented the expression of Bax while inducing an increase in expression of bcl2

Co- transplantation of bone marrow stromal cells with schwann cells evokes mechanical allodynia in the contusion model of spinal cord injury in rats

Several studies have shown that, although transplantation of neural stem cells into the contusion model of spinal cord injury [SCI] promotes locomotor function and improves functional recovery, it induces a painful response, Allodynia. Different studies indicate that bone marrow stromal cells [BMSCs] and Schwann cells [SCs] can improve locomotor recovery when transplanted into the injured rat spinal cord. Since these cells are commonly used in cell therapy, we investigated whether co-transplantation of these cells leads to the development of Allodynia. In this experimental research, the contusion model of SCI was induced by laminectomy at the T8-T9 level of the spinal cord in adult female wistar rats [n=40] weighting [250-300g] using the New York University Device. BMSCs and SCs were cultured and prelabeled with 5-bromo-2-deoxyuridine [BrdU] and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiI] respectively. The rats were divided into five groups of 8 including: a control group [laminectomy only], three experimental groups [BMSC, SC and Co-transplant] and a sham group. The experimental groups received BMSCs, SCs, and BMSCs and SCs respectively by intraspinal injection 7 days after injury and the sham group received serum only. Locomotion was assessed using Basso, Beattie and Bresnahan [BBB] test and Allodynia by the withdrawal threshold test using Von Frey Filaments at 1, 7, 14, 21, 28, 35, 42, 49 and 56 days after SCI. The statistical comparisons between groups were carried out by using repeated measures analysis of variances [ANOVA]. Significant differences were observed in BBB scores in the Co- transplant group compared to the BMSC and SC groups [p< 0.05]. There were also significant differences in the withdrawal threshold means between animals in the sham group and the BMSC, SC and the Co-transplant groups [p<0.05].BBB scores and withdrawal threshold means showed that co-transplation improved functioning but greater Allodynia compared to the other experimental groups. The present study has shown that, although transplantation of BMSCs, SCs and a combination of these cells into the injured rat spinal cord can improve functional recovery, it leads to the development of mechanical Allodynia. This finding indicates that strategies to reduce Allodynia in cell transplantation studies are required

Evaluation of Bcl-2 family gene expression in hippocampus of 3, 4-methylenedioxymethamphetamine treated rats

3,4-methylenedioxymethamphetamine [MDMA] is an illicit, recreational drug that causes cellular death and neurotoxicity. This study evaluates the effects of different doses of MDMA on the expression of apoptosis-related proteins and genes in the hippocampus of adult rats. In this experimental study, a total of 20 male Sprague Dawley rats [200-250 g] were treated with MDMA [0, 5, 10, 20 mg/kg i.p. twice daily] for 7 days. Seven days after the last administration of MDMA, the rats were killed. Bax and Bcl-2 genes in addition to protein expressions were detected by western blot and reverse transcription polymerase chain reaction [RT-PCR].Results were analyzed using one-way ANOVA and p

Zingiber officinale alters 3,4-methylenedioxymeth amphetamine-induced neurotoxicity in rat brain

The spice Zingiber officinale or ginger possesses antioxidant activity and neuroprotective effects. The effects of this traditional herbal medicine on 3,4-methylenedioxymethamphetamine [MDMA] induced neurotoxicity have not yet been studied. The present study considers the effects of Zingiber officinale on MDMA-induced spatial memory impairment and apoptosis in the hippocampus of male rats. In this experimental study, 21 adult male Sprague Dawley rats [200-250 g] were classified into three groups [control, MDMA, and MDMA plus ginger]. The groups were intraperitoneally administered 10 mg/kg MDMA, 10 mg/kg MDMA plus 100 mg/kg ginger extract, or 1 cc/kg normal saline as the control solution for one week [n=7 per group]. Learning memory was assessed by Morris water maze [MWM] after the last administration. Finally, the brains were removed to study the cell number in the cornu ammonis [CA1] hippocampus by light microscope, Bcl-2 by immunoblotting, and Bax expression by reverse transcription polymerase chain reaction [RT-PCR]. Data was analyzed using SPSS 16 software and a one-way ANOVA test. Escape latency and traveled distances decreased significantly in the MDMA plus ginger group relative to the MDMA group [p<0.001]. Cell number increased in the MDMA plus ginger group in comparison to the MDMA group. Down-regulation of Bcl-2 and up-regulation of Bax were observed in the MDMA plus ginger group in comparison to the MDMA group [p<0.05]. Our findings suggest that ginger consumption may lead to an improvement of MDMA-induced neurotoxicity

role of the A2A receptor in cell apoptosis caused by MDMA

Ecstasy, also known as 3, 4-methylenedioxymethamphetamine [MDMA], is a psychoactive recreational hallucinogenic substance and a major worldwide recreational drug. There are neurotoxic effects observed in laboratory animals and humans following MDMA use. MDMA causes apoptosis in neurons of the central nervous system [CNS]. Withdrawal signs are attenuated by treatment with the adenosine receptor [A2A receptor]. This study reports the effects of glutamyl cysteine synthetase [GCS], as an A2A receptor agonist, and succinylcholine [SCH], as an A2A receptor antagonist, on Sprague Dawley rats, both in the presence and absence of MDMA. In this experimental study, we used seven groups of Sprague Dawley rats [200-250 g each]. Each group was treated with daily intraperitoneal [IP] injections for a period of one week, as follows: i. MDMA [10 mg/kg]; ii. GCS [0.3 mg/kg]; iii. SCH [0.3 mg/kg]; iv. GCS + SCH [0.3 mg/kg each]; v. MDMA [10 mg/kg] + GCS [0.3 mg/kg]; vi. MDMA [10 mg/kg] + SCH [0.3 mg/kg]; and vi. normal saline [1 cc/kg] as the sham group. Bax [apoptotic protein] and Bcl-2 [anti-apoptotic protein] expressions were evaluated by striatum using RT-PCR and Western blot analysis. There was a significant increase in Bax protein expression in the MDMA+SCH group and a significant decrease in Bcl-2 protein expression in the MDMA+SCH group [p<0.05]. A2A receptors have a role in the apoptotic effects of MDMA via the Bax and Bcl-2 pathways. An agonist of this receptor [GCS] decreases the cytotoxcity of MDMA, while the antagonist of this receptor [SCH] increases its cytotoxcity

effects of cyclosporin-A on functional outcome and axonal regrowth following spinal cord injury in adult rats

It has been shown that the immunophilin ligands have the special advantage in spinal cord repair. In this study, the effects of cyclosporine A [CsA] on functional recovery and histological outcome were evaluated following spinal cord injury in rats. After spinal cord hemisection in thirty six adult female Sprague-Dawley rats [200- 250 g], treatment groups received CsA [2.5 mg/kg i.p.] at 15min and 24h after lesion [CsA 15min group and CsA 24h group] daily, for 8 weeks. Control and sham groups received normal saline and in sham operated animals the spinal cord was exposed in the same manner as treatment groups, but was not hemisected. Hindlimb motor function was assessed in 1, 3, 5 and 7 weeks after lesion, using locomotive rating scale developed by Basso, Bresnahan and Beattie [BBB]. Motor neurons were counted within the lamina IX of ventral horn and lesion size was measured in 5 mm of spinal lumbar segment with the epicenter of the lesion site. The mean number of motor neurons and the mean BBB scale in 3, 5 and 7 weeks in CsA 15min groups significantly increased compared to the control group. Although, the lesion size reduced in rats with CsA treatment compared to the control group, no significant difference was observed. Thus, it can be concluded that CsA can improve locomotor function and histological outcome in the partial spinal cord injury

Prenatal mercuric chloride exposure causes developmental deficits in rat cortex

Introduction: Environmental pollution with heavy metals such as mercury is a major health problem. Growing studies on the field have shown the deleterious effects of mercury on human and nonhuman nervous system, especially in infants, however the effects of prenatal exposure to mercuricchloride on cortical development are not yet well understood. The aim of this study was to investigate the effect of prenatal exposure to mercuric chloride on morphological characteristics of brain cortex. Methods: Mercuric chloride [2 mg/kg] or normal saline were injected [I.P.] to 36 Sprague – dawley rats in the 8th, 9th or 10th day of gestation. The embryos were surgically removed in the 15th day of gestation, and brain cortices were studied by histological techniques. Results: Histological studies showed that embryos of mercuric chloride treated rats hadcortical neuronal disarrangement withdifferent orientations of nuclei, increased diameter of cortex, increased mitosis of cells, increased cell death, decreased cellular density and increased intracellular space. Conclusion: These findings suggest some micro structural abnormalities in cortical regions after prenatal exposure to mercuric chloride. These structural abnormalities may underliesome neurologic disturbances following mercury intoxication

Protective effects of N-Acetyl-L-cystein on 3,4-Methylene Dioxymethamphetamie-induced Neurotoxicity in Cerebellum of male rats

3-4, methylenedioxymethamphetamine [MDMA] causes apoptosis in nervous system and several studies suggest that oxidative stress contributes to MDMA-induced neurotoxicity. The aim of this study is to examine the effects of N-acetyl-L-Cystein [NAC] as an antioxidant on MDMA-induced apoptosis. 21 Sprague dawley male rats [200-250mg] were treated with MDMA [2x0,5mg/kg] or MDMA plus NAC [100mg/kg IP for 7 day]. After last administration of MDMA, rats were killed, cerebellum was removed and Bax and Bcl-2 expression was assessed by western blotting method. The results of this study showed that MDMA causes up-regulation of Bax and down-regulation of Bcl-2 and NAC administration attenuated MDMA-induced apoptosis. The present study suggests that NAC treatment may improve MDMA-induced neurotoxicity.

Comparison of transplantation of bone marrow stromal cells [BMSC] and stem cell mobilization by granulocyte colony stimulating factor after traumatic brain injury in rat

Recent clinical studies of treating traumatic brain injury [TBI] with autologous adult stem cells led us to compare effect of intravenous injection of bone marrow mesenchymal stem cells [BMSC] and bone marrow hematopoietic stem cell mobilization, induced by granulocyte colony stimulating factor [G-CSF], in rats with a cortical compact device. Forty adult male Wistar rats were injured with controlled cortical impact device and divided randomly into four groups. The treatment groups were injected with 2 x 10[6] intravenous bone marrow stromal stem cell [n = 10] and also with subcutaneous G-CSF [n = 10] and sham-operation group [n = 10] received PBS and [bromodeoxyuridine [Brdu]] alone, i.p. All injections were performed 1 day after injury into the tail veins of rats. All cells were labeled with Brdu before injection into the tail veins of rats. Functional neurological evaluation of animals was performed before and after injury using modified neurological severity scores [mNSS]. Animals were sacrificed 42 days after TBI and brain sections were stained by Brdu immunohistochemistry. Statistically, significant improvement in functional outcome was observed in treatment groups compared with control group [P<0.01]. mNSS showed no significant difference between the BMSC and G-CSF-treated groups during the study period [end of the trial]. Histological analyses showed that Brdu-labeled [MSC] were present in the lesion boundary zone at 42[nd] day in all injected animals. In our study, we found that administration of a bone marrow-stimulating factor [G-CSF] and BMSC in a TBI model provides functional benefits

Morphological identification of cell death in dorsal root ganglion neurons following peripheral nerve injury and repair in adult rat

Axotomy causes sensory neuronal loss. Reconnection of proximal and distal nerve ends by surgical repair improves neuronal survival. It is important to know the morphology of primary sensory neurons after the surgical repair of their peripheral processes. Animals [male Wistar rats] were exposed to models of sciatic nerve transection, direct epineurial suture repair of sciatic nerve, autograft repair of sciatic nerve, and sham operated. After 1 and 12 weeks of the surgery, the number of L5 dorsal root ganglion [DRG] and ultrastructure of L4-L5 DRG neurons was evaluated by fluorescence and electron microscopy, respectively. Nerve transection caused sensory neuronal loss and direct epineurial suture but no autograft repair method decreased it. Evaluation of morphology of the neurons showed classic features of apoptosis as well as destructive changes of cytoplasmic organelles such as mitochondria, rough endoplasmic reticulum and Golgi apparatus in primary sensory neurons. These nuclear and cytoplasmic changes in primary sensory neurons were observed after the surgical nerve repair too. The present study implies that the following peripheral nerve transection apoptosis as well as cytoplasmic cell death contributes to neuronal cell death and reconnection of proximal and distal nerve ends dose not prevent these processes