Pronounced α-Synuclein Pathology in a Seeding-Based Mouse Model Is Not Sufficient to Induce Mitochondrial Respiration Deficits in the Striatum and Amygdala.

Increasing evidence suggests that cross talk between α-synuclein pathology formation and mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson's disease (PD) and related synucleinopathies. While mitochondrial dysfunction is a well-studied phenomenon in the substantia nigra, which is selectively vulnerable in PD and some models thereof, less information is available in other brain regions that are also affected by synuclein pathology. Therefore, we sought to test the hypothesis that early α-synuclein pathology causes mitochondrial dysfunction and that this effect might be exacerbated in conditions of increased vulnerability in affected brain regions, such as the amygdala.

Chronic corticosterone aggravates behavioral and neuronal symptomatology in a mouse model of alpha-synuclein pathology.

Debilitating, yet underinvestigated nonmotor symptoms related to mood/emotion, such as depression, are common in Parkinson's disease. Here, we explore the role of depression and of the amygdala, a brain region robustly linked to mood/emotion, in synucleinopathy. We hypothesized that mood/emotional deficits might accelerate Parkinson's disease-linked symptomatology, including the formation of α-synuclein pathology.

Impact of propofol anaesthesia on cytokine expression profiles in the developing rat brain: a randomised placebo-controlled experimental in-vivo study.

Background: Recent experimental data indicate that volatile anaesthetics can induce a neuroinflammatory response in the central nervous system. The questions of to what extent this occurs in the developing brain and whether nonvolatile anaesthetics are also involved remain unanswered.

Objectives: The objective of this study is to investigate the impact of propofol anaesthesia on cytokine mRNA expression profiles in the neonatal brain at defined stages of the brain growth spurt.

Recombinant tissue plasminogen activator enhances microglial cell recruitment after stroke in mice.

The effect of recombinant human tissue plasminogen activator (rtPA) on neuroinflammation after stroke remains largely unknown. Here, we tested the effect of rtPA on expression of cellular adhesion molecules, chemokines, and cytokines, and compared those with levels of inflammatory cell recruitment, brain injury, and mortality over 3 days after transient middle cerebral artery occlusion (MCAO) in mice. Mortality was dramatically increased after rtPA treatment compared with saline treatment during the first day of reperfusion.

The prognostic significance of the serum biomarker heart-fatty acidic binding protein in comparison with s100b in severe traumatic brain injury.

The outcome after severe traumatic brain injury (TBI) is largely unfavorable, with approximately two thirds of patients suffering from severe disabilities or dying during the first 6 months. Existing predictive models displayed only limited utility for outcome prediction in individual patients. Time courses of heart-fatty acidic binding protein (H-FABP) and their association with outcome were investigated and compared with S100b.

Treatment with Evasin-3 reduces atherosclerotic vulnerability for ischemic stroke, but not brain injury in mice.

Neutrophilic inflammation might have a pathophysiological role in both carotid plaque rupture and ischemic stroke injury. Here, we investigated the potential benefits of the CXC chemokine-binding protein Evasin-3, which potently inhibits chemokine bioactivity and related neutrophilic inflammation in two mouse models of carotid atherosclerosis and ischemic stroke, respectively. In the first model, the chronic treatment with Evasin-3 as compared with Vehicle (phosphate-buffered saline (PBS)) was investigated in apolipoprotein E-deficient mice implanted of a 'cast' carotid device.

Matrix metalloproteinase 9 and cellular fibronectin plasma concentrations are predictors of the composite endpoint of length of stay and death in the intensive care unit after severe traumatic brain injury.

Background: The relationship between severe traumatic brain injury (TBI) and blood levels of matrix metalloproteinase-9 (MMP-9) or cellular fibronectin (c-Fn) has never been reported. In this study, we aimed to assess whether plasma concentrations of MMP-9 and c-Fn could have predictive values for the composite endpoint of intensive care unit (ICU) length of stay (LOS) of survivors and mortality after severe TBI. Secondary outcomes were the state of consciousness measured with the Glasgow Coma Scale (GCS) of survivors at 14 days and Glasgow Outcome Scale Extended (GOSE) at 3 months.

Increase of arginase activity in old apolipoprotein-E deficient mice under Western diet associated with changes in neurovascular unit.

Aging and atherosclerosis are well-recognized risk factors for cardiac and neurovascular diseases. The Apolipoprotein E deficient (ApoE-/-) mouse on a high-fat diet is a classical model of atherosclerosis, characterized by the presence of atherosclerotic plaques in extracranial vessels but not in cerebral arteries. Increase in arginase activity was shown to participate in vascular dysfunction in the peripheral arteries of atherosclerotic mice by changing the level of nitric oxide (NO).

Matrix metalloproteinase-9 concentration in the cerebral extracellular fluid of patients during the acute phase of aneurysmal subarachnoid hemorrhage.

Objectives: The pathogenesis of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) is multi-factorial and not completely elucidated. Matrix metalloproteinase-9 (MMP-9) might participate in wall remodeling leading to luminal narrowing. The authors investigated MMP-9 concentration in brain extracellular fluid of aSAH patients and assessed whether this enzyme could have a predictive value for the risk of DCI.

Recombinant tissue plasminogen activator induces blood-brain barrier breakdown by a matrix metalloproteinase-9-independent pathway after transient focal cerebral ischemia in mouse.

The role of the inducible matrix metalloproteinase (MMP)-9 in blood-brain barrier (BBB) disruption after ischemic stroke is well accepted. Recombinant tissue plasminogen activator (r-tPA) is the only approved thrombolytic treatment of ischemic stroke but r-tPA is potentially neurotoxic. Vasogenic edema after r-tPA treatment has been linked with an increase in cerebral MMP-9.

Effect of the duration of middle cerebral artery occlusion on the risk of hemorrhagic transformation after tissue plasminogen activator injection in rats.

Thrombolysis with tissue plasminogen activator increases the risk of brain hemorrhage after ischemic stoke. However, the relationship between the duration of ischemia and the risk of hemorrhagic transformation is still unclear. In the present study, we used a rat model of thrombolysis with tissue plasminogen activator after different periods of middle cerebral artery occlusion and we analyzed the effect of the duration of ischemia on the rate of hemorrhagic transformation, the extent of cerebral infarction and the degree of neurological impairment.

Delayed matrix metalloproteinase inhibition reduces intracerebral hemorrhage after embolic stroke in rats.

Hemorrhagic transformation (HT) and brain edema are life-threatening complications of recombinant tissue plasminogen activator (rt-PA)-induced reperfusion after ischemic stroke. The risk of HT limits the therapeutic window for reperfusion to 3 h after stroke onset. Pre-treatment with matrix metalloproteinase (MMP) inhibitors reduces HT and cerebral edema in experimental stroke.

Plasma concentrations of brain-derived neurotrophic factor in patients undergoing minor surgery: a randomized controlled trial.

We measured perioperative plasma concentrations of brain-derived neurotrophic factor (BDNF), a major mediator of synaptic plasticity in the central nervous system, in males, 30-65 years old, undergoing lumbar or cervical discotomy. Patients were randomly allocated to a general anesthetic with propofol induction and maintenance or with thiopental induction and isoflurane maintenance. BDNF plasma concentrations were measured before induction (baseline), 15 min after induction but before start of surgery, at skin closure, in the post-anesthetic care unit, and 24 h postoperatively.

Matrix metalloproteinase-9 deficiency has no effect on glial scar formation after transient focal cerebral ischemia in mouse.

Glial scar formation was investigated in wild-type and MMP-9 deficient mice during a period of 21 days after 45 min of focal cerebral ischemia by intraluminal thread occlusion of the middle cerebral artery. The results showed no differences in the kinetics of activation of microglia, oligodendrocyte precursors and reactive astrocytes and showed only a slight difference in the pattern of macrophage infiltration. These results suggest that a specific targeting of MMP-9, as a mean to prevent ischemia-induced blood-brain barrier disruption, would have no significant effects on the recruitment of cells involved in glial scar formation.

Persisting vasculitis after pneumococcal meningitis.

Introduction: Bacterial meningitis is associated with a high mortality and a high incidence of neurological sequelae. Parainfectious vasculitis leading to ischemic brain damage is a known complication of bacterial meningitis but its treatment is uncertain.

Methods And Results: We report the case of a 53-year-old man with pneumococcal meningitis who developed numerous ischemic lesions in the brainstem and basal ganglia caused by parainfectious vasculitis.

Epidural anaesthesia restores pancreatic microcirculation and decreases the severity of acute pancreatitis.

Aim: To investigate the effect of epidural anaesthesia (EA) on pancreatic microcirculation during acute pancreatitis (AP).

Methods: AP was induced by injection of sodium taurocholate into the pancreatic duct of Sprague-Dawley rats. To realize EA, a catheter was introduced into the epidural space between T7 and T9 and bupivacaine was injected.

Matrix metalloproteinases and diseases of the central nervous system with a special emphasis on ischemic brain.

Matrix metalloproteinases (MMPs) are involved in the pathogenesis of several diseases of the CNS, that share common pathophysiological processes, such as blood-brain barrier (BBB) disruption, oxidative stress, remodeling of the extracellular matrix (ECM) and inflammation. In ischemic brain injury, MMPs are implicated in various stages of the disease. Early after the onset of ischemia, MMPs contribute to the disruption of the BBB leading to vasogenic edema and to the influx of leucocytes into the CNS.

Role of matrix metalloproteinases in apoptosis after transient focal cerebral ischemia in rats and mice.

The involvement of matrix metalloproteinases (MMPs) in cerebral ischemia-induced apoptosis was investigated in a model of transient focal cerebral ischemia in rats treated intracerebroventricularly (i.c.v.

Neurodegeneration in striatum induced by the mitochondrial toxin 3-nitropropionic acid: role of matrix metalloproteinase-9 in early blood-brain barrier disruption?

Blood-brain barrier (BBB) dysfunction is a potential mechanism involved in progressive striatal damage induced by the mitochondrial excitotoxin, 3-nitropropionic acid (3-NP). After activation by proteases and free radicals, matrix metalloproteinases (MMPs), particularly MMP-9 and -2, can digest the endothelial basal lamina leading to BBB opening. Using CD-1 mice, we show that MMP-9 expression by zymography is increased in the injured striatum compared with the contralateral striatum 2 hr after 3-NP injection [133.