Albumin is known to have neuroprotective effects. The protein has a long half-life circulation, and its effects can therefore persist for a long time to aid in the recovery of brain ischemia. In the present study, we investigated the neuroprotective effects of human serum albumin (HSA) on brain hemodynamics. Albumin is administrated using repeated oral gavage to the rodents. Sprague-Dawley rats underwent middle cerebral artery occlusion procedures and served as a stroke model. Afterwards, 25% human serum albumin (1.25 g/kg) or saline (5 ml/kg) was orally administrated for 2 weeks in alternating days. After 2 weeks, the rodents were assessed for levels of brain ischemia. Our testing battery consists of behavioral tests and in vivo optical imaging sessions. Modified neurological severity scores (mNSS) were obtained to assess the levels of ischemia and the effects of HSA oral administration. We found that the experimental group demonstrated larger hemodynamic responses following sensory stimulation than controls that were administered with saline. HSA administration resulted in more significant changes in cerebral blood volume following direct cortical electric stimulation. In addition, the mNSS of the treatment group was lower than the control group. In particular, brain tissue staining revealed that the infarct size was also much smaller with HSA administration. This study provides support for the efficacy of HSA, and that long-term oral administration of HSA may induce neuroprotective effects against brain ischemia.
Administration, Oral* ; Animals ; Anoxia ; Behavior Rating Scale ; Blood Volume ; Brain Ischemia* ; Brain* ; Electric Stimulation ; Half-Life ; Hemodynamics ; Humans* ; Infarction, Middle Cerebral Artery ; Ischemia ; Neuroprotection ; Neuroprotective Agents ; Optical Imaging ; Rats* ; Rats, Sprague-Dawley ; Rodentia ; Serum Albumin* ; Stroke

A single exposure to stress can induce functional changes in neurons, potentially leading to acute stress disorder or post-traumatic stress disorder.In this study, we used in vivo wide-field optical mapping to simultaneously measure neural calcium signals and hemodynamic responses over the whole cortical area. We found that cortical mapping to whisker stimuli was altered under acute stress conditions. In particular, callosal projections in the anterior cortex (primary/secondary motor, somatosensory forelimb cortex) relative to barrel field (S1BF) of somatosensory cortex were weakened. On the contrary, the projections in posterior cortex relative to S1BF were mostly unchanged or were only occasionally strengthened. In addition, changes in intra-cortical connection were opposite to those in inter-cortical connection. Thus, the S1BF connections to the anterior cortex were strengthened while those to the posterior cortex were weakened. This suggests that the well-known barrel cortex projection route was enhanced. In summary, our in vivo wide-field optical mapping study indicates that a single acute stress can impact whole-brain networks, affecting both neural and hemodynamic responses.

Ischemia can cause decreased cerebral neurovascular coupling, leading to a failure in the autoregulation of cerebral blood flow. This study aims to investigate the effect of varying degrees of ischemia on cerebral hemodynamic reactivity using in vivo real-time optical imaging. We utilized direct cortical stimulation to elicit hyper-excitable neuronal activation, which leads to induced hemodynamic changes in both the normal and middle cerebral artery occlusion (MCAO) ischemic stroke groups. Hemodynamic measurements from optical imaging accurately predict the severity of occlusion in mild and severe MCAO animals. There is neither an increase in cerebral blood volume nor in vessel reactivity in the ipsilateral hemisphere (I.H) of animals with severe MCAO. The pial artery in the contralateral hemisphere (C.H) of the severe MCAO group reacted more slowly than both hemispheres in the normal and mild MCAO groups. In addition, the arterial reactivity of the I.H in the mild MCAO animals was faster than the normal animals. Furthermore, artery reactivity is tightly correlated with histological and behavioral results in the MCAO ischemic group. Thus, in vivo optical imaging may offer a simple and useful tool to assess the degree of ischemia and to understand how cerebral hemodynamics and vascular reactivity are affected by ischemia.
Animals ; Arteries ; Blood Volume ; Cerebrovascular Circulation ; Hemodynamics* ; Homeostasis ; Infarction, Middle Cerebral Artery* ; Ischemia ; Middle Cerebral Artery* ; Neurons ; Neurovascular Coupling ; Optical Imaging ; Rodentia* ; Stroke

Agmatine is a decarboxylated arginine by arginine decarboxylase. Agmatine is known to be a neuroprotective agent. It has been reported that agmatine works as a NMDA receptor blocker or a competitive nitric oxide synthase inhibitor in CNS injuries. In spinal cord injury, agmatine showed reduction of neuropathic pain, improvement of locomotor function, and neuroprotection. Macrophage is a key cellular component in neuroinflammation, a major cause of impairment after spinal cord injury. Macrophage has subtypes, M1 and M2 macrophages. M1 macrophage induces a pro-inflammatory response, but M2 inspires an anti-inflammatory response. In this study, it was clarified whether the neuroprotective effect of agmatine is related with the modulation of macrophage subdivision after spinal cord injury. Spinal cord injury was induced in rats with contusion using MASCIS. Animals received agmatine (100 mg/kg, IP) daily for 6 days beginning the day after spinal cord injury. The proportion of M1 and M2 macrophages are confirmed with immunohistochemistry and FACS. CD206+ & ED1+ cells were counted as M2 macrophages. The systemic treatment of agmatine increased M2 macrophages caudal side to epicenter 1 week after spinal cord injury in immunohistochemistry. M2 macrophage related markers, Arginase-1 and CD206 mRNA, were increased in the agmatine treatment group and M2 macrophage expressing and stimulated cytokine, IL-10 mRNA, also was significantly overexpressed by agmatine injection. Among BMPs, BMP2/4/7, agmatine significantly increased only the expression of BMP2 known to reduce M1 macrophage under inflammatory status. These results suggest that agmatine reduces impairment after spinal cord injury through modulating the macrophage phenotype.
Agmatine* ; Animals ; Arginine ; Contusions ; Immunohistochemistry ; Interleukin-10 ; Macrophages* ; N-Methylaspartate ; Neuralgia ; Neuroprotection ; Neuroprotective Agents ; Nitric Oxide Synthase ; Phenotype* ; Rats* ; RNA, Messenger ; Spinal Cord Injuries* ; Spinal Cord*

Several studies have reported that depression is prevalent in patients with diabetes or chronic kidney disease. However, the relationship between weight changes and the risk of depression has not been elucidated in patients with diabetic kidney disease (DKD). Methods: From the Korean National Health Insurance Service database, we selected 67,866 patients with DKD and body weight data from two consecutive health examinations with a 2-year interval between 2009 and 2012. Weight change over 2 years was categorized into five groups: ≥–10%, <–10% to ≥–5%, <–5% to <5%, ≥5% to <10%, and ≥10%. The occurrence of depression was monitored via the codes of International Statistical Classification of Diseases, 10th revision through the end of 2018. Results: During the 5.24-year follow-up, 17,023 patients with DKD developed depression. Weight change and the risk of depression had a U-shaped relationship: patients with ≥–10% weight change (hazard ratio [HR], 1.12) and those with ≥10% weight change (HR, 1.11) showed higher HRs for depression than those with <–5% to <5% weight change, even after adjusting for several confounding factors. In the subgroup analyses, the risk of depression tended to increase as weight gain or weight loss increased in all subgroups. Conclusion: Both weight loss and weight gain increased the risk of depression in patients with DKD.