Bradykinin-induced leukocyte- and platelet-endothelium interactions in the cerebral microcirculation.

Bradykinin is known for its pathophysiological role as mediator of inflammation. Following cerebral ischemia, bradykinin promotes the secondary brain damage through an increase of vascular permeability and brain edema formation, again hallmarks of inflammation. It is not clear, whether bradykinin also activates inflammatory cells and regulates microcirculatory blood flow in the brain.

Inflammatory response to nitrous oxide in the central nervous system.

Nitrous oxide is a widely used anesthetic gas. The aim of this study was to investigate the effect of this agent on inflammatory side effects in the brain. The cerebral microcirculation of Mongolian gerbils was investigated by fluorescent intravital microscopy for up to 7 h after induction of anesthesia.

Arteriovenous transit time as a measure for microvascular perfusion in cerebral ischemia and reperfusion.

Objective: The aim of this study was to measure microvascular perfusion (MVP) on the brain surface in global ischemia and reperfusion by means of intravital fluorescence microscopy.

Methods: Global ischemia was induced in gerbils for 15 minutes with 3 hours of reperfusion. The passage of a rhodamine bolus (25 mul intravenously) from an arteriole to a venule was analyzed by intravital fluorescence microscopy through a cranial window.

Activation of leukocyte-endothelial interactions and reduction of selective neuronal death after global cerebral ischemia.

The role of leukocyte-endothelial interactions (LEI) as part of the inflammatory response after global cerebral ischemia (GCI) is hardly understood and may be detrimental as well as beneficial. Objective of the current study was to investigate the cause-effect relationship of activated leukocytes for the development of ischemic brain damage. Mongolian gerbils were subjected to 15 min of global cerebral ischemia.

Effect of oxidative stress on glial cell volume.

Cytotoxic brain edema is a major contributor of tissue damage following cerebral ischemia and traumatic brain injury. The pathophysiology of cytotoxic edema formation is still not well understood. Although it is widely believed that oxidative stress causes cytotoxic brain edema, experimental proof is lacking.

Special aspects of severe head injury: recent developments.

Trauma in general, and head injury in particular, is the most frequent cause of mortality and morbidity in those aged up to 45 years. Outcome from severe head injury depends on the nature and severity of the primary lesion, and the manifestations of secondary brain damage of extra- and intracranial origin. The most important sequela is cerebral ischaemia resulting from intracranial hypertension caused by, for example, traumatic brain swelling or intracranial haemorrhage and/or systemic complications, of which arterial hypotension is the most significant.

Modified labeling technique for in vivo visualization of platelets in the cerebral microcirculation of Mongolian gerbils.

Activation of platelets induces interactions with platelets, endothelial cells, and leukocytes. In vivo observation of these interactions in the cerebral microcirculation is rare. The purpose of the present study was to develop a model enabling the in vivo observation of platelet kinetics in the cerebral microcirculation.

Lactacidosis-induced glial cell swelling depends on extracellular Ca2+.

Cerebral tissue acidosis following ischemia or traumatic brain injury contributes to cytotoxic brain edema formation. In vitro lactacidosis induces swelling of glial cells by intracellular Na+- and Cl--accumulation by the Na+/H+-antiporter, Cl-/HCO3--antiporters and the Na+-K+-2Cl--cotransport. The present study aimed to elucidate whether mechanisms of lactacidosis-induced glial swelling are dependent on intra- or extracellular Ca2+-ions.

Arterial hypotension triggers perifocal depolarizations and aggravates secondary damage in focal brain injury.

Perifocal depolarizations (PFD) have been observed after traumatic brain injury, are known to disturb cerebrovascular reactivity and thus may contribute to the morphological consequences of brain injury. In this investigation, the role of PFD was studied in focal brain lesions with/without induction of delayed hypotension. Cerebral freeze lesions were induced in anesthetized normotensive rats that underwent perfusion fixation of brains 5 min, 4 h or 24 h after lesioning, respectively, to obtain quantitative histopathology.

Neuroprotective effects of a postischemic treatment with a bradykinin B2 receptor antagonist in a rat model of temporary focal cerebral ischemia.

Bradykinin, an endogenous nonapeptide produced by activation of the kallikrein-kinin system, promotes neuronal tissue damage as well as disturbances in blood-brain barrier function through activation of B2 receptors. In a rat model of focal cerebral ischemia, blockade of B2 receptors before initiation of ischemia with the B2 receptor antagonist, LF 16-0687 Ms, afforded substantial neuroprotection. In order to assess the potential clinical value of this approach, we evaluated the effect of LF 16-0687 Ms given at reperfusion following focal cerebral ischemia on local cerebral blood flow (LCBF), neurological outcome, and infarct size.

Effect of P-selectin inhibition on leukocyte-endothelium interaction and survival after global cerebral ischemia.

Cerebral ischemia induces activation of leukocyte-endothelium interactions requiring upregulation of specific adhesion molecules including the selectins. The aim of the current study was to elucidate the therapeutic potency of P-selectin blockade on microcirculatory disturbances and secondary brain damage after global cerebral ischemia. Global cerebral ischemia for 15 minutes was induced in Mongolian gerbils.

Cluster analysis: a useful tool for the analysis of cerebral laser-Doppler scanning data.

Laser-Doppler (LD) fluxmetry (LDF) is a widely used method for the measurement of relative tissue perfusion. Assessing LD-flux at multiple locations using a scanning technique greatly reduces movement artefacts and makes repetitive measurements at the same location possible. However, measurements in brain are often confounded by superficial cortical vessels.

Dose finding study of intravenous magnesium sulphate in transient focal cerebral ischemia in rats.

Background: During many neurovascular procedures temporary occlusion of cerebral arteries is inevitable. Neuroprotective drugs may reduce the risk of cerebral infarction in this situation. Increasing evidence indicates neuroprotective properties of magnesium in cerebral ischemia.

Neuroprotection in ischemic stroke--combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia.

We have recently demonstrated marked neuroprotective efficacy of a combination therapy with magnesium (calcium- and glutamate-antagonist), tirilazad (antioxidant) and mild hypothermia (MTH) in a rat model of transient focal cerebral ischemia. In the present study, we investigated MTH under conditions of permanent focal cerebral ischemia. In part I, 20 Sprague-Dawley rats were subjected to 6 h of permanent, laser-Doppler flowmetry (LDF) controlled middle cerebral artery occlusion (MCAO).

Prospective documentation and analysis of the pre- and early clinical management in severe head injury in southern Bavaria at a population based level.

Treatment of patients suffering from severe head injury is so far restricted to general procedures, whereas specific pharmacological agents of neuroprotection including hypothermia have not been found to improve the outcome in clinical trials. Albeit effective, symptomatic measures of the preclinical rescue of patients (i.e.

Identification of brain tissue necrosis by MRI: validation by histomorphometry.

The volume of an experimental necrotic lesion of the cortex expands up to 400% of its initial size within the first 24 h after the insult. Lesion expansion, a clinically well known phenomenon, is often accompanied by perifocal brain edema and consequently difficult to image and to analyze by magnetic resonance imaging (MRI). Therefore we aimed to validate a T(2)-weighted spin echo sequence upon its ability to distinguish necrotic from edematous brain tissue.

Correlation of lesion volume and brain swelling from a focal brain trauma.

Brain edema and secondary growth of a traumatic brain tissue necrosis are important manifestations of secondary brain damage and of prognostic significance in severe head injury. Aim of the current study was to analyze the interdependency of the resulting brain swelling from the size of the focal traumatic lesion. Male Sprague-Dawley rats were intubated and mechanically ventilated.

Therapeutical efficacy of a novel non-peptide bradykinin B2 receptor antagonist on brain edema formation and ischemic tissue damage in focal cerebral ischemia.

Objective: Bradykinin has been identified as a mediator of secondary brain damage in acute insults. We currently studied neuroprotective properties of a bradykinin B2 receptor antagonist (LF16-0687 Ms) in transitory focal cerebral ischemia to assess infarct formation and the development of brain edema.

Material And Methods: 55 Rats were subjected to 90 min of MCA-occlusion.

Effect of decompression craniotomy on increase of contusion volume and functional outcome after controlled cortical impact in mice.

If, how, and when decompressive craniotomy should be used for the treatment of increased intracranial pressure after traumatic brain injury are widely discussed clinical subjects. Despite the large number of clinical studies addressing this issue, experimental evidence of a beneficial or detrimental role of decompressive craniotomy after brain trauma is sparse. Therefore, we investigated the influence of craniotomy on intracranial pressure, contusion volume, and functional outcome in a model of traumatic brain injury in mice.

Secondary growth of a cortical necrosis: effect of NOS inhibition by aminoguanidine post insult.

Background: A cortical tissue necrosis from a focal freezing injury expands to 140% of its initial volume within 24 hrs in rats. Previous studies of our laboratory have shown that administration of the NOS inhibitor aminoguanidine (AG) prior to trauma attenuates this process of secondary brain damage. Objective of the present study was to analyse whether this agent is also protective when treatment commences after the insult.

Relative cerebral blood flow during the secondary expansion of a cortical lesion in rats.

The size of a cerebral contusion is not finite at the moment of trauma, but liable to secondary increase during the following hours and days. In the present study we investigated whether this phenomenon may be related to changes in cortical blood flow (cCBF). In rats a cortical lesion grew to 140% of its initial volume during the first 24 h after injury.

Neuroprotective efficacy of intra-arterial and intravenous magnesium sulfate in a rat model of transient focal cerebral ischemia.

Background: Many neurovascular procedures necessitate temporary occlusion of cerebral arteries. In this situation neuroprotective drugs may increase the safety of the procedures. Magnesium may inhibit ischemic damage by anti-excitotoxic, calcium channel blocking and vasodilatory action.

Bradykinin antagonists reduce leukocyte-endothelium interactions after global cerebral ischemia.

The aim of the present study was to evaluate the influence of bradykinin on microcirculatory changes and outcome after global cerebral ischemia (15 minute) in Mongolian gerbils. The cerebral microcirculation was investigated by fluorescent intravital microscopy. Survival and functional outcome was evaluated up to 4 d after ischemia.

Impact of the endothelin-A receptor antagonist BQ 610 on microcirculation in global cerebral ischemia and reperfusion.

The role of endogenous endothelin-1 in mediating microcirculatory disturbances after global cerebral ischemia was investigated in Mongolian gerbils. The pial microcirculation was studied by intravital fluorescent microscopy before, during, and up to 3 h after occlusion of both carotid arteries for 15 min. Pretreatment was achieved with the peptidergic selective endothelin-A (ET-A) receptor antagonist BQ 610.

Effects of LF 16-0687 Ms, a bradykinin B(2) receptor antagonist, on brain edema formation and tissue damage in a rat model of temporary focal cerebral ischemia.

Bradykinin, an endogenous nonapeptide produced by activation of the kallikrein-kinin system, promotes neuronal tissue damage as well as disturbances in blood-brain barrier function through activation of B(2) receptors. LF 16-0687 Ms, a non-peptide competitive bradykinin B(2) receptor antagonist, was recently found to decrease brain swelling in various models of traumatic brain injury. We have investigated the influence of LF 16-0687 Ms on the edema formation, neurological outcome, and infarct size in temporary focal cerebral ischemia in rats.