Dexmedetomidine Stereotaxic Injection Alleviates Neuronal Loss Following Bilateral Common Carotid Artery Occlusion via Up-Regulation of BDNF Expression.

BACKGROUND/AIM: Neurogenesis is an important process in the recovery from neurological damage caused by ischemic lesions. Endogenous neurogenesis is insufficient to restore neuronal damage following cerebral ischemia. Dexmedetomidine (DEX) exerts neuroprotective effects against cerebral ischemia and ischemia/reperfusion injury. DEX promotes neurogenesis, including neuronal proliferation and maturation in the hippocampus. In a previous study, we showed that early neurogenesis increased 3 days after bilateral common carotid artery occlusion (BCCAO). In this study, we investigated the effect of DEX on neurogenesis 3 days after BCCAO. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats (7-8 weeks old) were used as a BCCAO model. Right and left common carotid arteries of the rats were occluded using 4-0 silk sutures. Two hours after surgery, an intracranial DEX injection was administered to rats that underwent surgery using a stereotaxic injector. Brains were obtained from control and BCCAO rats 3 days after surgery. Immunohistochemistry was performed on the cortex and dentate gyrus of the hippocampus using a NeuN antibody. Western blot was performed with HIF1α and brain-derived neurotrophic factor (BDNF) antibodies. RESULTS: The number of mature neurons decreased 3 days after BCCAO, but DEX treatment alleviated neural loss in the parietal cortex and hippocampus. Up-regulation of BDNF was also observed after dexmedetomidine treatment. CONCLUSION: Stereotaxic injection of dexmedetomidine alleviates neural loss following BCCAO by up-regulating BDNF expression.

Differential Expression of Pax6 Following Bilateral Common Carotid Artery Occlusion.

BACKGROUND/AIM: Chronic cerebral hypoperfusion causes neuronal damage involving cognitive impairment and development of dementia. Permanent bilateral common carotid artery occlusion (BCCAO) in rat models is used to study chronic cerebral hypoperfusion. Pax6 is used as an early neurogenesis marker which affects the maturation of neuronal cells. However, the expression of PAX 6 after BCCAO is not well understood. In this study, we investigated the expression of PAX6 in the neurogenic zones after BCCAO to evaluate the effects of Pax6 on chronic hypoperfusion. MATERIALS AND METHODS: Chronic hypoperfusion was induced by BCCAO. Common carotid artery was laid parallel to the vagus nerve and separated from it. Both arteries were occluded using 4-0 silk sutures. Rats who underwent bi-common carotid artery occlusion formed in the BCCAO group, while unoperated rats served as the control group. Brain samples were obtained on days 3 and 14 after BCCAO and subjected to immunohisto-chemistry with NeuN and western blotting for Pax6 and HIF1α. RESULTS: Compared to the control, the expression of Pax6 increased three days after surgery but did not differ on day 14, while that of NeuN showed the opposite trend. The expression of HIF1α increased three days after surgery. CONCLUSION: Bilateral common carotid artery occlusion induced early neurogenesis at three days after BCCAO but this result was not maintained at fourteen days after BCCAO.

Is the popliteus tendon always inserted antero-inferiorly 18.5 mm from the lateral collateral ligament of the femur? Magnetic resonance imaging and cadaveric evaluations.

BACKGROUND: The aim of this study was to analyze the locations of the femoral attachments of the popliteus tendon (PT) and lateral collateral ligament (LCL) via magnetic resonance imaging (MRI) and cadaveric dissection in a Korean population and compare with literature standards to determine whether variability exists. METHODS: We retrospectively analyzed knee MRIs from 87 cases selected from January 2017 to December 2018. The relationship between the femoral attachment of PT and LCL was analyzed by MRI using PACS and Image J. In addition, the femoral attachments of each structure were identified and marked in 14 unpaired human cadaveric knees. Three-dimensional models were reconstructed, and the surface area, location and distances were analyzed. RESULTS: On MRI, the femoral attachment of PT was located at mean distances of 0.89 mm posterior and 9.35 mm inferior to the LCL femoral attachment. We identified three groups of PT locations relative to the LCL on MRI evaluation: parallel (63%), posterior (29%), and anterior (8%). On cadaveric evaluation, the femoral attachment of the PT was located at mean distances of 0.77 mm posterior and 8.90 mm inferior to the LCL femoral attachment. We also identified three groups of PT locations relative to the LCL on cadaveric evaluation: parallel (43%), posterior (36%), and anterior (21%). CONCLUSIONS: Based on both MRI and cadaveric evaluations in a Korean population, the femoral attachment of the PT is located just distal to and posterior to the LCL. The differences between the centroids of the femoral attachments of the two structures was approximately 9.7 mm, suggesting that racially based anatomical differences of the posterolateral corner may exist.

Differential Expression of BDNF and BIM in Streptozotocin-induced Diabetic Rat Retina After Fluoxetine Injection.

BACKGROUND: Chronic diabetic retinopathy (DR) is a diabetic complication that causes blindness. Brain-derived neurotrophic factor (BDNF) expression is induced by fluoxetine. We observed the effects of fluoxetine on a streptozotocin (STZ)-induced diabetic rat model in this study. MATERIALS AND METHODS: Rats were divided into three groups: Control, diabetic (65 mg/kg STZ injection), and diabetic with fluoxetine injection (20 mg/kg/week, six times). Western blotting was performed using anti-BDNF and anti-hexaribonucleotide-binding protein-3. Expression of BCL2 apoptosis regulator-like protein 11 (BIM) was analysed using a reverse transcription-polymerase chain reaction. RESULTS: BDNF levels were significantly higher in the diabetic group treated with fluoxetine than in the untreated diabetic group. BIM expression was higher in the diabetic group than in the control group. BIM gene expression was lower in fluoxetine-treated diabetic group than in the untreated diabetic group. CONCLUSION: Fluoxetine had an anti-apoptotic effect with upregulation of BDNF expression in retina of rats with STZ-induced diabetes.

IGF-1 Protects Neurons in the Cortex and Subventricular Zone in a Periventricular Leucomalacia Model.

BACKGROUND/AIM: Chronic cerebral hypoperfusion affects early and mature neurons in the subventricular zone (SVZ) and cerebral cortex. Herein, we investigated the effects of insulin-like growth factor-1 (IGF-1), a neurogenesis-promoting agent, on neurons in these regions in periventricular leucomalacia (PVL) model rats. MATERIALS AND METHODS: Following right carotid artery ligation, the rats were placed in a hypoxia chamber and injected with recombinant IGF-1 (0.1 and 1 µg/µl). Their brain sections were immunohistochemically analysed using anti-nestin and anti-NeuN antibodies. RESULTS: The numbers of early-neuronal cells in the SVZ and mature neurons in the cerebral cortex were higher and lower, respectively, in the PVL group than in the control group. The number of NeuN-positive cells was significantly higher in the IGF-treated group than in the PVL group. CONCLUSION: PVL increased the number of early neuronal cells in the SVZ, reducing the survival of mature neurons in the cerebral cortex; IGF-1 reversed these effects.

Brain-derived neurotrophic factor in non-proliferative diabetic retinopathy with diabetic macular edema.

PURPOSE: To investigate aqueous humor (AH) and serum levels of brain-derived neurotrophic factor (BDNF) in non-proliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME). METHODS: The prospective study consists of 20 patients with DME NPDR, 20 patients with no-DME NPDR, and 20 healthy control subjects. Serum and AH samples were obtained during cataract surgery and intravitreal injection. Serum and AH levels of BDNF were measured by enzyme-linked immunosorbent assay. RESULTS: The mean serum levels of BDNF were lower in both NPDR groups compared to the control group (DME NPDR group, p = 0.015; no-DME NPDR group, p = 0.024). Furthermore, the mean serum level of BDNF was lower in the DME NPDR group compared to the no-DME NPDR group (p = 0.041). The mean AH levels of BDNF were significantly reduced in both NPDR groups compared to the control group (DME NPDR group, p < 0.001; no-DME NPDR group, p = 0.006). Further, the mean AH level of BDNF was significantly lower in the DME NPDR group compared to the no-DME NPDR group (p = 0.037). CONCLUSION: Serum and AH levels of BDNF were reduced in NPDR patients with DME than without DME.

Immunoreactivity of MAPK Signaling in a Rat Model of Intrauterine Growth Retardation Induced by Uterine Artery Ligation.

BACKGROUND/AIM: Intrauterine growth retardation (IUGR) causes very low birth weight and is related to the morbidity and mortality of the newborn. In our previous study, expression of brain-derived neurotrophic factor (BDNF) was found reduced in the cerebral cortex and dentate gyrus of fetuses with IUGR. BDNF protected cortical neurons against hypoxic injury via activation of the extracellular signal-related kinase (ERK) pathway. The aim of the current study was to observe the immunoreactivity of ERK in mature neurons and proliferating cells. MATERIALS AND METHODS: Uterine artery ligation was performed at 17 days of gestation (dg). Rat fetuses were obtained at 21 dg using cesarean section. Fetuses were designated either to the growth retardation (GR) group when removed from the horn with uterine artery ligation, or to the control group when removed from the other horn with the untied artery. Immunohistochemistry was performed with primary antibodies on paraffin-embedded forebrain sections. RESULTS: The density and proportion of cells expressing PCNA, ERK, and phosphate ERK in the subventricular zone (SVZ) was not different between the control and GR group. The density and proportion of NeuN- and phosphate ERK-positive cells in the cerebral parietal cortex was lower in the GR group, compared to the control group. CONCLUSION: Although IUGR had no effect on the proliferation of cells in the SVZ, it reduced neuronal survival in the cerebral parietal cortex, which was associated with the decrease of pERK-positive cell density and proportion in the cerebral cortex.

Differential Expression of Vascular Endothelial Growth Factor in the Cortex and Hippocampus upon Cerebral Hypoperfusion.

BACKGROUND/AIM: Vascular endothelial growth factor (VEGF) provides tolerance against ischemic brain injury, yet, the pattern of VEGF expression in the neurogenic zones following chronic cerebral hypoperfusion has not been studied. Here we evaluated the immunoreactivity of VEGF in a rat model of chronic cerebral hypoperfusion. MATERIALS AND METHODS: Chronic hypoperfusion was induced by bilateral common carotid artery ligation in rats. Immunohistochemistry was performed against hypoxia-inducible factor-1α (HIF-1α) and VEGF on brain sections. RESULTS: The density of HIF1α-positive cells in the hypoxia group was increased in the cerebral cortex and hippocampus. Further, the density of VEGF-positive cells was significantly higher in the hypoxia group compared to the control group in the cerebral cortex whereas it was similar in the subventricular zone, and in the dentate gyrus in the hippocampus between the two groups. CONCLUSION: The pattern of VEGF expression varies in different brain regions following chronic cerebral hypoperfusion.