0000000000124391
AUTHOR
Nikolaus Plesnila
Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice
The weight-drop model is used widely to replicate closed-head injuries in mice; however, the histopathological and functional outcomes may vary significantly between laboratories. Because skull fractures are reported to occur in this model, we aimed to evaluate whether these breaks may influence the variability of the weight-drop (WD) model. Male Swiss Webster mice underwent WD injury with either a 2 or 5 mm cone tip, and behavior was assessed at 2 h and 24 h thereafter using the neurological severity score. The expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 genes was m…
Plasminogen activator inhibitor‐1 augments damage by impairing fibrinolysis after traumatic brain injury
Objective Plasminogen activator inhibitor-1 (PAI-1) is the key endogenous inhibitor of fibrinolysis, and enhances clot formation after injury. In traumatic brain injury, dysregulation of fibrinolysis may lead to sustained microthrombosis and accelerated lesion expansion. In the present study, we hypothesized that PAI-1 mediates post-traumatic malfunction of coagulation, with inhibition or genetic depletion of PAI-1 attenuating clot formation and lesion expansion after brain trauma. Methods We evaluated PAI-1 as a possible new target in a mouse controlled cortical impact (CCI) model of traumatic brain injury. We performed the pharmacological inhibition of PAI-1 with PAI-039 and stimulation b…
Mechanisms of Cell-Volume Regulation in the Central Nervous System
Function and viability of every cell is dependent on the proper control of its shape and volume. In the brain, which is protected by a rigid outer shell, cell-volume regulation is of particular importance, since large volume changes affect cerebral perfusion and, hence, function. Neuronal activation leads to constant changes of the ionic and metabolic composition of the brain’s extracellular space. These changes are buffered by astrocytes on the expense of constant changes in cell volume. Under pathological conditions, the ability of astrocytes to maintain the homeostasis of the brain is overwhelmed and permanent cell swelling, cytotoxic edema, occurs. The current chapter describes the prin…
In vitro and in vivo porphyrin accumulation by C6 glioma cells after exposure to 5-aminolevulinic acid
Several malignant tissues synthesize endogenous porphyrins after exposure to 5-aminolevulinic acid (5-ALA). The present experiments have been designed to elucidate whether the C6 glioma cell, a model cell for human malignant glioma, similarly synthesizes porphyrins when exposed to 5-ALA, and whether specific synthesis occurs when C6 cells are inoculated into rat brains to form a tumor. In this situation the blood-brain barrier may interfere with 5-ALA availability, and spreading of porphyrins with edema outside the tumor may occur. Flow cytometry is used to determine the course of cell volume and porphyrin fluorescence intensities in cultured C6 cells which are incubated in 1 mM 5-ALA. For …
Hypertonic fluid resuscitation from subarachnoid hemorrhage in rats: A comparison between small volume resuscitation and mannitol
Abstract Objective Death and severe morbidity after subarachnoid hemorrhage (SAH) are mainly caused by global cerebral ischemia through increased intracranial pressure (ICP) and decreased cerebral blood flow (CBF). We have recently demonstrated neuroprotective effects of small volume resuscitation (7.5% saline in combination with 6% dextran 70) in an animal model of SAH, leading to normalization of increased ICP, reduced morphological damage and improved neurological recovery. In the present study, we compared the concept of small volume resuscitation represented by two clinically licenced hypertonic–hyperoncotic saline solutions with the routinely used hyperosmotic agent–mannitol–and inves…