Early detection of cognitive decline in mild cognitive impairment and Alzheimer's disease with a novel eye tracking test.

Due to an increasing number of dementia patients, the development of a rapid and sensitive method for cognitive assessment is awaited. Here, we examined the usefulness of a novel and short (3 min) eye tracking device to evaluate the cognitive function of normal control (NC, n = 52), mild cognitive impairment (MCI, n = 52), and Alzheimer's disease (AD, n = 70) subjects. Eye tracking total score declined significantly in MCI (**p < 0.01 vs NC) and AD (**p < 0.01 vs NC, ##p < 0.01 vs MCI), and correlated well with the mini-mental state examination (MMSE) score (r = 0.57, *p < 0.05). Furthermore, the eye tracking test, especially memory and deductive reasoning tasks, effectively discriminated NC, MCI and AD. The present novel eye tracking test clearly discriminated cognitive functions among NC, MCI, and AD subjects, thereby providing an advantage for the early detection of MCI and AD in screening.

A Polyphenolic Complex Attenuates Inflammatory Response and Blood- Brain Barrier Disruption.

BACKGROUND: Cerebral ischemia causes a strong inflammatory response. Neumentix is a dietary supplement containing 14.9% rosmarinic acid and 29.9% total phenolic content, which has been proved to be beneficial against inflammatory response. Therefore, Neumentix's effect on anti-inflammatory and blood brain barrier (BBB) disruption in transient middle cerebral artery occlusion (tMCAO) model mice is investigated in this study. METHODS: After the pretreatment of vehicle or Neumentix 134 mg/kg/d, intraperitoneal injection (i.p.) (containing rosmarinic acid 20 mg/kg/d) for 14 days, mice were subjected to tMCAO for 60 min and kept receiving vehicle or Neumentix daily 5 days afterward. RESULTS: Neumentix treatment ameliorated neurobehavioral impairment in the corner test (5d after tMCAO, **P<0.01), reduced infarct volume (#P<0.05), suppressed expression of ionized calciumbinding adapter molecule-1 (Iba-1), tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) (###P<0.001), and improved the integrity of BBB (§P<0.05) at 5 days after tMCAO. CONCLUSION: The present study provided an evidence of Neumentix's anti-inflammatory and neuroprotection effect against BBB disruption on experimental tMCAO model mice, suggesting that Neumentix could be a potential therapeutic agent for stroke.

Bone Marrow Stromal Cell Transplantation Drives Molecular Switch from Autophagy to the Ubiquitin-Proteasome System in Ischemic Stroke Mice.

BACKGROUND: Bone marrow stromal cell (BMSC) transplantation is a promising therapeutic approach for cerebral ischemia, as it elicits multiple neuroprotective effects. However, it remains unclear how BMSC transplantation modulates the ubiquitin-proteasome system (UPS) and autophagy under cerebral ischemia. METHODS: In the present study, an intermediate level of cerebral ischemia (30 minutes) was chosen to examine the effect of BMSC transplantation on the molecular switch regulating UPS and autophagy. BMSC or vehicle was stereotactically injected into the penumbra 15 minutes after sham operation or transient middle cerebral artery occlusion (tMCAO). RESULTS: Thirty minutes of tMCAO artery occlusion significantly increased TUNEL-, ubiquitin-, and p62-positive cells (which peaked at 72 hours, 2 hours, and 2 hours after reperfusion, respectively) and ratios of both BAG3/BAG1 and LC3-II/LC3-I at 24 hours after reperfusion. However, intracerebral injection of BMSCs significantly reduced infarct volume and numbers of TUNEL- and p62-positive cells, and improved BAG3/BAG1 and LC3-II/LC3-I ratios. In addition, observed increases in ubiquitin-positive cells 2 hours after reperfusion were slightly suppressed by BMSC transplantation. CONCLUSIONS: These data suggest a protective role of BMSC transplantation, which drove the molecular switch from autophagy to UPS in a murine model of ischemic stroke.

Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) with Limbic Encephalitis.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory central nervous system disorder that mainly involves in the brainstem, basal ganglia and cerebellum. We herein report the case of a patient with CLIPPERS, which was diagnosed based on the clinical and radiological features. After initially responded to steroid treatment, the patient developed limbic encephalitis. The patient presented with memory disturbance, a delirious state and emotional incontinence. A cerebrospinal fluid study revealed interleukin-6 elevation and enhanced bilateral hippocampal lesions were observed on MRI. The patient was successfully treated with methylprednisolone pulse therapy. This is the first case of CLIPPERS with limbic encephalitis involving the bilateral hippocampus.

Successful Delayed Aortic Surgery for a Patient with Ischemic Stroke Secondary to Aortic Dissection.

The diagnosis of aortic dissection (AD) is sometimes difficult within the limited time window of recombinant tissue plasminogen activator (tPA) for ischemic stroke (IS). A 60-year-old man developed sudden left hemiparesis due to IS. During tPA infusion, his blood pressure dropped and consciousness declined. After transfer to our hospital, carotid duplex ultrasonography led to a diagnosis of AD. Emergency surgery was postponed because of the risk of hemorrhagic transformation. The patient successfully underwent aortic surgery on day 5 and was discharged with a remarkable improvement in his symptoms. Delayed surgery may avoid hemorrhagic transformation in patients with AD-induced IS who have received tPA.