Stroke is the leading cause of death and neurological disorders worldwide. However, diagnostic techniques and treatments for stroke patients are still limited for certain types of stroke. Intensive research has been conducted so far to find suitable diagnostic techniques and treatments, but so far there has been no success. In recent years, various studies have drawn much attention to the clinical value of utilizing the mechanism of exosomes, low toxicity, biodegradability, and the ability to cross the blood–brain barrier. Recent studies have been reported on the use of biomarkers and protective and recovery effects of exosomes derived from stem cells or various cells in the diagnostic stage after stroke. This review focuses on publications describing changes in diagnostic biomarkers of exosomes following various strokes and processes for various potential applications as therapeutics.

Post-traumatic stress disorder (PTSD) is a well-known mental illness, which is caused by various stressors, including memories of past physical assaults and psychological pressure. It is diagnosed as a mental and behavioral disorder, but increasing evidence is linking it to the immune system and inflammatory response. Studies on the relationship between inflammation and PTSD revealed that patients with PTSD had increased levels of inflammatory cytokine biomarkers, such as interleukin-1, interleukin-6, tumor necrosis factor-α, nuclear factor-κB, and C-reactive protein, compared with healthy controls. In addition, animal model experiments imitating PTSD patients suggested the role of inflammation in the pathogenesis and pathophysiology of PTSD. In this review, we summarize the definition of PTSD and its association with increased inflammation, its mechanisms, and future predictable diseases and treatment possibilities. We also discuss anti-inflammatory treatments to address inflammation in PTSD.

Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (miR-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. MiR-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60(+) cells in colonies unless miR-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the miR-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental.

Patients with vascular dementia, caused by cerebral ischemia, experience long-term cognitive impairment due to the lack of effective treatment. The mechanisms of and treatments for vascular dementia have been investigated in various animal models; however, the insufficient information on gene expression changes that define pathological conditions hampers progress. To investigate the underlying mechanism of and facilitate treatment development for vascular dementia, we established a mouse model of chronic cerebral hypoperfusion, including bilateral carotid artery stenosis, by using microcoils, and elucidated the molecular pathway underlying vascular dementia development. Rho-associated protein kinase (ROCK) 1/2, which regulates cellular structure, and inflammatory cytokines (IL-1 and IL-6) were upregulated in the vascular dementia model. However, expression of claudin-5, which maintains the blood–brain barrier, and MAP2 as a nerve cell-specific factor, was decreased in the hippocampal region of the vascular dementia model. Thus, we revealed that ROCK pathway activation loosens the tight junction of the blood–brain barrier and increases the influx of inflammatory cytokines into the hippocampal region, leading to neuronal death and causing cognitive and emotional dysfunction. Our vascular dementia model allows effective study of the vascular dementia mechanism. Moreover, the ROCK pathway may be a target for vascular dementia treatment development in the future.

The low-density-lipoprotein receptor (LDLr) removes low-density lipoprotein (LDL), an endovascular transporter that carries cholesterol from the bloodstream to peripheral tissues. The maintenance of cholesterol content in the brain, which is important to protect brain function, is affected by LDLr. LDLr co-localizes with the insulin receptor and complements the internalization of LDL. In LDLr deficiency, LDL blood levels and insulin resistance increase, leading to abnormal cholesterol control and cognitive deficits in atherosclerosis. Defects in brain cholesterol metabolism lead to neuroinflammation and blood–brain-barrier (BBB) degradation. Moreover, interactions between endoplasmic reticulum stress (ER stress) and mitochondria are induced by ox-LDL accumulation, apolipoprotein E (ApoE) regulates the levels of amyloid beta (Aβ) in the brain, and hypoxia is induced by apoptosis induced by the LDLr defect. This review summarizes the association between neurodegenerative brain disease and typical cognitive deficits.

Cerebral small vessel disease (CSVD) is a group of pathologies that affect the cerebral blood vessels. CSVD accounts for 25% of strokes and contributes to 45% of dementia. However, the pathogenesis of CSVD remains unclear, involving a variety of complex mechanisms. CSVD may result from dysfunction in the glymphatic system (GS). The GS contains aquaporin-4 (AQP-4), which is in the perivascular space, at the endfeet of the astrocyte. The GS contributes to the removal of waste products from the central nervous system, occupying perivascular spaces and regulating the exchange and movement of cerebrospinal fluid and interstitial fluid. The GS involves astrocytes and aquaporin channels, which are components of the blood–brain barrier, and problems with them may constitute the pathogenesis of CSVD. Vascular risk factors, including diabetes, dilate the perivascular space, disrupting the glymphatic system and the active regulation of AQP-4. CSVD exacerbation due to disorders of the GS is associated with multiple vasculopathies. Dysfunction of the glymphatic system and AQP-4 interferes with the functioning of the blood–brain barrier, which exacerbates CSVD. In a long-term follow-up of CSVD patients with microbleeds, lacunar infarcts, and white matter hyperintensity, several vascular risk factors, including hypertension, increased the risk of ischemic stroke. Dysfunction of the GS may be the cause of CSVD; however, the underlying treatment needs to be studied further.