ISSN:1015-9770    

DOI:10.1159/000108235

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Although there is currently no generally accepted consensus on the management of acute ischaemic stroke, several organisations are working towards producing guidelines for this disease. A major step in ensuring the rapid presentation and treatment of sufferers would be to promote stroke as a medical emergency, especially, since early thrombolytic therapy has been shown to be the first successful treatment of stroke. Public and professional education would also raise the profile of this condition and improve knowledge of the stages of treatment. The instigation of stroke units, teams or even stroke pathways would offer optimal patient care and provide the facilities necessary for effective diagnosis and management. Increasing patient and physician awareness of stroke and encouraging prompt patient referral to such units may mean that patients are best placed to receive early treatment with the neuroprotective agents currently in the late stages of clinical evaluation.

ISSN:1015-9770    

DOI:10.1159/000108236

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Focal ischaemic injury in the brain is related to both the intensity and the duration of the decrement in cerebral blood flow. The ischaemic penumbra, an area characterised by levels of blood flow slightly greater than the ischaemic core itself, is a zone exhibiting preserved or even accentuated metabolic rate, apparently driven by recurrent ischaemic depolarisations. Excitatory amino acid neurotransmitter release and raised levels of oxygen radical activity occur within it. The penumbra represents that region of the focal ischaemic lesion which is potentially amenable to metabolic neuroprotection, and several classes of neuroprotective agents are currently under clinical evaluation for stroke. As the untreated penumbra deteriorates over time, animal studies indicate that therapy should be administered within a therapeutic window of no more than 3–6 h from stroke onset if it is to be successful.

ISSN:1015-9770    

DOI:10.1159/000108237

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

There are many neuroprotectants currently under evaluation for the treatment of acute ischaemic stroke, but encouraging clinical trials have been rare. Neuroprotective drugs interfere with various stages of the ischaemic cascade leading to irreversible tissue damage, and are not thought to affect bleeding. While trials of sodium/calcium channel modifiers have been problematic, there are hopes that the phenytoin derivative fos-phenytoin will yield interesting findings in phase II trials. Studies of several N-methyl-D-aspartate antagonists, such as selfotel and dextrorphan, have been suspended because of unacceptable side-effect profiles, while those with other agents, notably cerestat, are continuing. Gamma-aminobutyric acid agonists can induce hyperpolarisation, and thereby counteract the depolarisation seen in the ischaemic cascade. A safety analysis of such an agonist, the anti-epilepsy drug clomethiazole, has shown it is well tolerated and the results of a large phase III trial are anticipated. Lubeluzole, an inhibitor of glutamate-induced nitric oxide-related neurotoxicity, is another agent which has just completed phase III trials. Early studies have been promising and have shown that it is a well tolerated neuroprotectant.

ISSN:1015-9770    

DOI:10.1159/000108238

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Lubeluzole, the S-isomer of a novel difluorobenzothiazole, is a neuroprotective compound aimed at the treatment of acute ischaemic stroke. In a photochemical stroke model in rats, in which a neurological test was designed that is also relevant to other stroke models, intravenous posttreatment with lubeluzole stereoselectively rescues sensorimotor function (time window of 6 h) and reduces infarct size. Posttreatment with lubeluzole also reduces infarct size after middle cerebral artery occlusion in rats, attenuates delayed neuronal death after global ischaemia, and may also act on mechanisms of cerebral oedema. The compound normalizes peri-infarct neuronal excitability and blocks the rise of peri-infarct extracellular concentration of glutamate. Lubeluzole downregulates the nitric oxide synthase (NOS) pathway leading to neurotoxicity and neuronal death. NOS pathway modulation may contribute to the neuroprotective properties of lubeluzole.

ISSN:1015-9770    

DOI:10.1159/000108239

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Lubeluzole, the S-isomer of a novel difluorobenzothiazole, is a neuroprotective compound aimed at the treatment of acute ischaemic stroke. In a photochemical stroke model in rats, in which a neurological test was designed that is also relevant to other stroke models, intravenous posttreatment with lubeluzole stereoselectively rescues sensorimotor function (time window of 6 h) and reduces infarct size. Posttreatment with lubeluzole also reduces infarct size after middle cerebral artery occlusion in rats, attenuates delayed neuronal death after global ischaemia, and may also act on mechanisms of cerebral oedema. The compound normalizes peri-infarct neuronal excitability and blocks the rise of peri-infarct extracellular concentration of glutamate. Lubeluzole downregulates the nitric oxide synthase (NOS) pathway leading to neurotoxicity and neuronal death. NOS pathway modulation may contribute to the neuroprotective properties of lubeluzole.

ISSN:1015-9770    

DOI:10.1159/000315514

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

While clinical studies of neuroprotectant therapy are necessary to study adverse events and correct dosing regimens, animal studies can investigate the mechanism of action, efficacy and therapeutic window of these agents. A rat model of photothrombotic stroke has shown that lubeluzole, 0.31 mg/kg/h, reduces sensorimotor deficit and infarct size. Further trials in rats with middle cerebral artery occlusion have confirmed these findings, and have shown lubeluzole to be effective in severe ischaemia. Studies in delaying the administration of lubeluzole found that maximal effect was derived when this agent was given within 30 min of the onset of ischaemia. There is also evidence that lubeluzole may be effective in treating reperfusion injury, and that it may be beneficial to combine it with reperfusion therapies, such as thrombolysis.

ISSN:1015-9770    

DOI:10.1159/000108240

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The neuroprotectant lubeluzole is a benzothiazole compound in late clinical evaluation for the treatment of acute ischaemic stroke. In experimental animals, lubeluzole prevents extracellular glutamate increase following ischaemia, inhibits glutamate-induced nitric oxide-related neurotoxicity and normalises neuronal excitability in the peri-infarct region. Animal models have shown lubeluzole to decrease infarct size following middle cerebral artery occlusion. Promising results in phase I trials of cardiac safety led to a phase II study investigating the effect of lubeluzole, 10 or 20 mg/day, on mortality and neurological and functional recovery in acute ischaemic stroke. Despite an increased mortality rate in the 20 mg/day group, later confirmed as an imbalance of randomisation unrelated to the drug, this trial showed that lubeluzole, 10 mg/day, was well tolerated and reduced mortality. A phase III trial has been recently completed and it is hoped that its results will confirm these findings.

ISSN:1015-9770    

DOI:10.1159/000108241

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:1015-9770    

DOI:10.1159/000108417

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Transcranial color-coded duplex sonography (TCCD) is a new ultrasound technique that adds color-coding of the frequency- or power-based Doppler signal and B-mode imaging to conventional transcranial Doppler sonography (TCD). As conventional TCD this technique identifies stenoses, occlusions and vasospasm of the major basal cerebral arteries. The additions visualize the anatomy and flow direction of the basal cerebral arteries, the ventricular system, parenchymal and bony structures. Thus potentially hazardous compression tests to identify cerebral arteries are rarely necessary, and ultrasonic assessment of cross-flow through the circle of Willis becomes more reliable. Moreover, estimates of insonation angles and measurements of angle-corrected flow velocities become feasible. TCCD may visualize larger (>1 x 1 cm) supratentorial hematomas with subcortical location, and provide incidental diagnosis of cerebral arteriovenous malformations, aneurysms, and hydrocephalus, but is inferior to neuroradiological techniques. The main limitation of TCCD is the acoustic window that may prevent transtemporal insonation in up to 30% of cases. Transpulmonary contrast agents may permit the examination of such patients. Power-based TCCD, used alone or in combination with echo contrast agents or three-dimensional ultrasound imaging, represent important future developments of TCCD.

ISSN:1015-9770    

DOI:10.1159/000108167

出版商:S. Karger AG    

年代:1997

数据来源: Karger