Tom Cadoux-Hudson

Magnesium protection against in vitro cerebral vasospasm after subarachnoid haemorrhage

Mg 2+ has recently been proposed for the treatment of cerebral vasospasm and is known to dilate vessels. In this study, we examine the effects of Mg 2+ on in vitro vasospasm using CSF from vasospastic subarachnoid haemorrhage patients with vasospasm (CSF v ). Oxygen consumption and isometric force measurements in the porcine carotid artery were used to assess the contractile and metabolic status of the vessels responses to CSF v and the effect of Mg 2+. Mg 2+ caused a dose dependant decrease in tension following contraction by CSF v. Mg 2+ (12 mM) caused a normalization of relaxation rate in tissue exposed to CSF v, caused a significant decrease in basal oxygen consumption, as well as significantly decreasing the rate of oxygen consumption of the porcine carotid artery when stimulated by CSF (0.70 - 0.12 versus. 0.46 - 0.1 w mol O 2 min -1 g -1 ). Acute Mg 2+ addition demonstrated the most effective protection using an assay based on CSF v contraction. These results suggest that Mg 2+ can protect vascular smooth muscle exposed to CSF v by benefiting contractile behaviour and metabolism of the arteries.

Role of ischaemia in the genesis of oedema surrounding meningiomas assessed using magnetic resonance imaging and spectroscopy

Oedema surrounding meningiomas is well known, but its pathogenesis remains obscure. Perfusion and metabolism in this peritumoural parenchyma were studied preoperatively in eight patients using magnetic resonance imaging, dynamic perfusion scanning and proton spectroscopy. Relative cerebral blood volumes (CBV) and metabolite ratios were calculated for the tumour and peritumoural brain. All meningiomas showed gadolinium enhancement, high choline (Ch), low creatine (Cr) and low N-acetyl aspartate (NAA) [Ch: (Ch + Cr) 0.67, SD 0.13, NAA: (Ch + Cr) 0.18, SD 0.15]. Lactate was present in four tumours [lactate: (Ch + Cr) 0.32, SD 0.27]. Extremely low gadolinium passage and low CBV were seen in the 2 cm peritumoural region, with elevated lactate [lactate: (Ch + Cr) 0.26, SD 0.18]. Four centimetres from tumour margin the CBV was still reduced (65, SD 20% with less lactate [lactate: (Ch + Cr) 0.12, SD 0.01]. Relative CBV is reduced around meningiomas and is associated with lactate, suggesting that oligaemia and altered metabolism may be part of the pathology in peritumoural oedema. Such changes may be important in determining functional recovery after surgery.

The stimulation of vascular smooth muscle oxidative metabolism by CSF from subarachnoid haemorrhage patients increases with Fisher and WFNS grades.

Summaryu2003The purpose of this paper is to present an in vitro method for examining cerebral vasospasm after subarachnoid haemorrhage (SAH) which correlates to the patients condition. The O2 consumption of the porcine carotid artery was monitored, using an oxygen electrode, after exposure to cerebrospinal fluid (CSF) from patients who had a SAH. The vessels were exposed to CSF from SAH patients at a 1 in 30 dilution. Force measurements were carried out using freeze-dried CSF, reconstituted in the organ bath equivalent to undiluted CSF. These observations were then compared to the patients condition.u2003We divided the patient CSF samples into those that stimulated oxygen consumption above 0.4 μM/min/g dry wt, and those that did not. It was found that there was a correlation between the stimulation of oxygen consumption and the Fisher grade as well as the World Federation of Neurosurgeons Grading System (WFNS) for the patients. Of the CSF tested, 24 stimulated oxygen consumption above our cut off, and 8 did not (0.84±0.34, n=24 compared with the rate of 0.27±0.1 μmol/min/g dry wt, respectively; SD n=8) at 180 minutes. We then examined the Fisher Grades of these two groups, the results were 3.21±0.88 vs 2.25±0.83 respectively (SD p≤0.01). When examining the WFNS System we found a similar difference between the groups that stimulated respiration and those who did not (WFNS Grades of 2.64±1.1 vs. 1.43±0.53; p≤0.01). The observed stimulation of oxygen consumption also correlated with tension generation in vitro.u2003The CSF from subarachnoid haemorrhage patients stimulates the oxygen consumption of the porcine carotid artery. This stimulation correlated to the WFNS and Fisher Grades of the patients and can be performed using 1:30 dilution of CSF. We conclude that the metabolic changes that occur in the vessels during vasospasm are important parameters for assessing cerebral vasospasm.

In Vitro Therapy with Dobutamine, Isoprenaline and Sodium Nitroprusside Protects Vascular Smooth Muscle Metabolism from Subarachnoid Haemorrhage Induced Cerebral Vasospasm

Summaryu2003Background. The cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients with cerebral vasospasm stimulates vasoconstriction and oxygen consumption in the porcine carotid artery in vitro. Stimulation of oxygen consumption has been used as an in vitro model of vasospasm to assess the relative benefits of nimodipine, isoprenaline, dobutamine, and sodium nitroprusside (SNP).u2003Method. Samples of human CSF were obtained from SAH patients and applied to de-endothelialised porcine carotid artery. Stimulation of oxygen consumption (as an in vitro marker for a stimulation of the vessels) was monitored and the effects of SNP, isoprenaline, dobutamine or nimodipine were measured.u2003Findings. The CSF from SAH patients with evidence of vasospasm stimulated oxygen consumption to 0.91±0.17 (μ M O2/min/g dry wt, ± SD p≤ 0.01) and CSF from SAH patients without vasospasm did not significantly stimulate oxygen consumption 0.27±0.02, with 0.23±0.03 (μ M O2/min/g dry wt) being an unstimulated rate of respiration for the porcine carotid artery. SNP, isoprenaline or dobutamine significantly (p≤ 0.01) decreased the stimulation of oxygen consumption of the porcine carotid artery whereas nimodipine did not. In a cohort of 41 SAH patients who received nimodipine alone or nimodipine and dobutamine, the in hospital mortality rate of the patients who received only nimodipine was 42% as compared to an in hospital mortality rate of 17% in the nimodipine plus dobutamine group P≤ 0.076).u2003Interpretation. The in vivo data on the 41 patients is not statistically significant, so further studies are required to determine if the differences are important. SNP, isoprenaline and dobutamine significantly decreased oxygen consumption of the porcine carotid arteries exposed to CSF from SAH patients who had vasospasm whereas nimodipine did not. Our in vitro results suggest that these compounds require further study in patients with SAH who are at risk for vasospasm because they may have a direct benefit for the vasospastic arteries.

Reversible brain injury in a head-injured patient identified by magnetic resonance imaging and spectroscopy.

Serial MRI studies of a severely head-injured patient showed extensive diffusion abnormalities lasting for 40 days. These were related to initial perfusion abnormalities and improved in parallel with clinical status. Spectroscopy showed diffuse damage and pH changes. Together these data support a role for ischaemia in head injury.

Early detection of cerebral microbleeds following traumatic brain injury using MRI in the hyper-acute phase

Highlights • Traumatic cerebral microbleeds (TCMBS) can be identified using susceptibility weighted imaging in the first few hours after injury.• TCMBs are a useful indicator of severity in this time frame.• The presence of TCMBs is an early indicator of injury severity following trauma.• There is a relationship between decreasing size of TCMBs and recovery.