Microglia through MFG-E8 signaling decrease the density of degenerating neurons and protect the brain from the development of cortical infarction after stroke.

Neuronal loss is a hallmark of stroke and other neurodegenerative diseases, and as such, neuronal loss caused by microglia has been thought to be a contributing factor to disease progression. Here, we show that microglia indeed contribute significantly to neuronal loss in a mouse model of stroke, but this microglial-dependent process of neuronal clearance specifically targets stressed and degenerating neurons in the ischemic cortical region and not healthy non-ischemic neurons. Nonspecific stimulation of microglia decreased the density of neurons in the ischemic cortical region, whereas specific inhibition of MFG-E8 signaling, which is required for microglial phagocytosis of neurons, had the opposite effect.

Application of project-based service-learning courses in medical education: trials of curriculum designs during the pandemic.

Background: Due to COVID-19, face-to-face service activities in service-learning courses have become unfeasible. To address this challenge, this study aims to integrate project-based learning into medical education's service-learning curriculum. This study also seeks to evaluate the effectiveness of this instructional approach and identify factors that influence its success.

Blood-Brain Barrier Disruption in Preclinical Mouse Models of Stroke Can Be an Experimental Artifact Caused by Craniectomy.

The pathophysiological features of ischemia-related blood-brain barrier (BBB) disruption are widely studied using preclinical stroke models. However, in many of these models, craniectomy is required to confirm arterial occlusion via laser Doppler flowmetry or to enable direct ligation of the cerebral artery. In the present study, mice were used to construct a distal middle cerebral artery occlusion (dMCAO) model, a preclinical stroke model that requires craniectomy to enable direct ligation of the cerebral artery, or were subjected to craniectomy alone.

Anterograde regulation of mitochondrial genes and FGF21 signaling by hepatic LSD1.

Mitochondrial biogenesis and function are controlled by anterograde regulatory pathways involving more than 1000 nuclear-encoded proteins. Transcriptional networks controlling the nuclear-encoded mitochondrial genes remain to be fully elucidated. Here, we show that histone demethylase LSD1 KO from adult mouse liver (LSD1-LKO) reduces the expression of one-third of all nuclear-encoded mitochondrial genes and decreases mitochondrial biogenesis and function.

Propofol Pretreatment Fails to Provide Neuroprotection Following a Surgically Induced Brain Injury Rat Model.

Neurosurgical procedures are associated with unintentional damage to the brain during surgery, known as surgically induced brain injuries (SBI), which have been implicated in orchestrating structural and neurobehavioral deterioration. Propofol, an established hypnotic anesthetic agent, has been shown to ameliorate neuronal injury when given after injury in a number of experimental brain studies. We tested the hypothesis that propofol pretreatment confers neuroprotection against SBI and will reduce cerebral edema formation and neurobehavioral deficits in our rat population.

Thrombin Preconditioning in Surgical Brain Injury in Rats.

The surgical brain injury model replicates neurosurgical brain parenchymal damage. Postsurgical brain edema correlates with postoperative neurological dysfunction. Intranasal administration is a proven method of delivering therapies to brain tissue.

Granulocyte-colony stimulating factor in combination with stem cell factor confers greater neuroprotection after hypoxic-ischemic brain damage in the neonatal rats than a solitary treatment.

Neonatal hypoxia-ischemia (HI) is a devastating condition resulting in neuronal cell death and often culminates in neurological deficits. Granulocyte-colony stimulating factor (G-CSF) has been shown to have neuroprotective activity via inhibition of apoptosis and inflammation in various stroke models. Stem cell factor (SCF) regulates hematopoietic stem cells in the bone marrow and has been reported to have neuroprotective properties in an experimental ischemic stroke model.

Treatment with sodium orthovanadate reduces blood-brain barrier disruption via phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphorylation in experimental subarachnoid hemorrhage.

Attenuation of blood-brain barrier (BBB) disruption is one of the therapeutic candidates for treatment of subarachnoid hemorrhage (SAH). In this study, the protective effect of sodium orthovanadate (SOV) on BBB disruption was investigated in SAH using the endovascular perforation model. Fifty-five rats were randomly assigned to sham-operated, SAH treated with saline (as a vehicle), or 10 mg/kg SOV groups and were evaluated for neurofunction and Evans blue dye extravasation.

Prolonged exposure to isoflurane ameliorates infarction severity in the rat pup model of neonatal hypoxia-ischemia.

The neonatal hypoxia-ischemia rat model referred to as the Rice-Vannucci model is extensively used to study perinatal hypoxia-ischemia and child brain injury. One of the major weaknesses of this model is its inconsistency of brain infarction among animals. We hypothesize that the inconsistency of infarction is caused by prolonged operation time and therefore isoflurane exposure.

Endoscopic surgical treatment for pituitary apoplexy in three elderly patients over the age of 80.

Objectives: As the population continues to live longer, the diagnosis of pituitary adenoma-induced apoplexy becomes more common in the elderly. The standard treatment options for pituitary apoplexy are debatable. Although there is little information regarding the treatment of pituitary apoplexy in elderly patients, the optimal treatment needs to be determined for this age group.

Cerebral amyloid angiopathy-related microhemorrhages in Alzheimer's disease: a review of investigative animal models.

There is a growing understanding of cerebral amyloid angiopathy (CAA), which accounts for the majority of primary lobal intracerebral hemorrhages (ICH) among the elderly [1] and is cited as the cause of 20% of spontaneous ICHs in patients over 70 years of age [2]. The basis for this disease process is the deposition and formation of eventually destructive amyloid plaques in the walls of brain vessels, predominantly arterial but not excluding venules and capillaries [3]. Investigation of the pathophysiology and therapies for CAA-associated hemorrhages have been made possible through animal models utilizing species that develop CAA in a similar fashion to humans, such as the squirrel monkey, rhesus monkey, dog and mutant and transgenic mouse strains, which exhibit the age-related development of amyloid plaques, progressive neurodegeneration and CAA-associated hemorrhages.

Comparison of different preclinical models of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the most devastating type of stroke. It is characterized by spontaneous bleeding in brain parenchyma and is associated with a high rate of morbidity and mortality. Presently, there is neither an effective therapy to increase survival after intracerebral hemorrhage nor a treatment to improve the quality of life for survivors.

History of preclinical models of intracerebral hemorrhage.

In order to understand a disease process, effective modeling is required that can assist scientists in understanding the pathophysiological processes that take place. Intracerebral hemorrhage (ICH), a devastating disease representing 15% of all stroke cases, is just one example of how scientists have developed models that can effectively mimic human clinical scenarios. Currently there are three models of hematoma injections that are being used to induce an ICH in subjects.

Comparison Evans Blue injection routes: Intravenous versus intraperitoneal, for measurement of blood-brain barrier in a mice hemorrhage model.

Aims: Intracerebral hemorrhage is one of the most devastating subtypes of stroke, leaving survivors with severe neurological deficits. Disruption of the blood brain barrier (BBB) following hemorrhage results in the development of vasogenic brain edema, a most life-threatening event after such events as intracerebral hemorrhage (ICH). The Evans Blue assay is a popular method for the quantification of BBB disruption.

Heat shock protein 70 upregulation by geldanamycin reduces brain injury in a mouse model of intracerebral hemorrhage.

Unlabelled: This study investigated the effect of geldanamycin post-treatment on the development of secondary brain injury and neurological deficits in a mouse model of intracerebral hemorrhage. CD-1 mice received stereotactic injection of collagenase type VII into the right basal ganglia. Treatment groups were administered 1 mg/kg (low dose) or 10 mg/kg (high dose) of geldanamycin.