Ulrich-Wilhelm Thomale

Neuroprotective Effect of Melatonin on Cortical Impact Injury in the Rat

Summaryu2003The pineal hormone melatonin is a highly efficient physiological scavenger of free radicals involved in secondary brain damage. A variety of experimental studies have demonstrated a neuroprotective effect for melatonin, based on its antioxidant activity. The purpose of the present study was to investigate the time-dependency and a possible protective effect of exogenous melatonin in the cortical impact model in rats. The protective effect was quantified determining contusion volume, brain edema and brain water content.u200345 anesthetized male Sprague-Dawley rats (250–350 mg) were subjected to cortical impact injury of moderate severity (7 m/s, deformation 2 mm). Melatonin (100 mg/kg bw i.p.), or a vehicle was injected 20 min before trauma, immediately after, and 1 and 2 hours after trauma during daytime and nighttime. Posttraumatic lesion volume using hematoxylin-eosin staining, hemispheric swelling, brain water content, cerebral perfusion pressure and intracranial pressure 24 hours after injury were investigated.u2003Melatonin, given during nighttime, significantly reduced contusion volume corresponding to a mean reduction of contusion volume of 27% (placebo, n=7: 41.9±5.2 mm3, melatonin, n=8: 30.5±4.2 mm3, p<0.05). Given during daytime, the reduction in contusion volume was not significant (placebo, n=8: 42.1±5.1 mm3, melatonin, n=8: 35.9±2.2 mm3, reduction of 15%, p=0.08, n.s.). Hemispheric swelling was unchanged by melatonin treatment. Mean arterial blood pressure and rectal temperature remained stable before and after the cortical impact injury and injection of melatonin. This study shows that melatonin significantly reduces contusion volume with major effects during night.

Magnetic Resonance Imaging Studies with Cluster Algorithm for Characterization of Brain Edema after Controlled Cortical Impact Injury (CCII)

Objective of this study was the characterization of traumatic brain injury induced by a Controlled Cortical Impact with magnetic resonance imaging techniques. The impact was applied to the intact dura of the left hemisphere in Sprague-Dawley rats. The pneumatic impactor was accelerated to a velocity of 7 m/s contusing the left temporo-parietal hemisphere to a depth of 2 mm. Posttraumatic hemispheric swelling and water content were determined gravimetrically, Evans Blue extravasation photometrically, and volume of ischemia by TTC-staining and planimetry. Magnetic resonance imaging was performed by a Bruker biospec 24/40, 90 min, 24 and 72 h post trauma using a T2w RARE sequence, a T1w sequence, before and after application of contrast agent, and a set of diffusion weighted images for calculation of ADC-maps. Data analysis was performed using a cluster algorithm enabling to interpret corresponding image pairs simultaneously. T2w imaging indicates the maximum edema about 24 h post trauma. Blood-brain barrier damage, detected by T1w imaging, is more predominant in the early posttraumatic phase. The cluster algorithm detects different edema components: from the necrotic core to the perifocal vasogenic rim. MRI in combination with the cluster algorithm will hopefully be a valuable tool in testing neuroprotective agents.

Visualization of rat pial microcirculation using the novel orthogonal polarized spectral (OPS) imaging after brain injury

Recently, the novel optical system, orthogonal polarized spectral (OPS) imaging was developed to visualize microcirculation. Investigation of changes in microcirculation is essential for physiological, pathophysiological, and pharmacological studies. In the present study applicability of OPS imaging was assessed to study pial microcirculation in normal and traumatized rat brain. High quality images of rat pial microcirculation in normal and traumatized rats were generated with the OPS imaging, allowing to easily differentiate arterioles and venules with the dura remaining intact. In non-traumatized rats, mean vessel diameter of arterioles and venules of five different cortical regions was 19.1+/-2.7 and 22.2+/-1.4 microm, respectively. In the early phase following focal cortical contusion vessel diameter was significantly decreased in arterioles by 28% while diameter in venules was significantly increased by 27%. For technical reasons velocity in arterioles was not measurable. In venules, mean flow velocity of 0.68+/-0.08 mm/s was significantly decreased by 50% at 30 min after trauma. OPS imaging is an easy to use optical system allowing to generate high quality images and to reliably investigate pial microcirculation without having to remove the dura. This technique opens the possibility to perform longitudinal studies investigating changes in pial microcirculation.

Cerebral metabolism and intracranial hypertension in high grade aneurysmal subarachnoid haemorrhage patients.

We evaluated the effect of intracranial hypertension on cerebral metabolism in patients with high grade aneurysmal subarachnoid hemorrhage (SAH) using bedside cerebral microdialysis (MD). Thirty-six patients with SAH were studied and classified into two groups (intracranial pressure, ICP > 20 mmHg, n = 25) and (ICP < 20 mmHg, n = 11). ICP was monitored hourly using an intraventricular drainage (n = 36). The MD catheter was placed after aneurysm clipping into the vascular territory of interest and was perfused with Ringers solution (0.3 microl/min). The MD samples were collected hourly for measurements of glucose, lactate, and glutamate (CMA 600, Sweden). Lactate/pyruvate ratio was also calculated. To calculate group specific differences, the 24 hours median values of the first 7 days after SAH were compared. Differences were considered statistically significant at P < 0.05. Patient groups were comparable for age, severity of SAH, Fishers grade and duration of MD sampling. In patients with ICP > 20 mmHg from day 1 to 7 after SAH, extracellular concentrations of glucose were significantly lower, while the lactate/ pyruvate ratio was higher compared to SAH patients with normal ICP values. The differences between groups in glutamate levels was only significant on day 1 after SAH due to high inter-individual differences. We concluded that intracranial hypertension in associated with an anaerobic cerebral metabolism indicated cerebral ischemia in high grade SAH patients.

Norepinephrine is Superior to Dopamine in Increasing Cortical Perfusion Following Controlled Cortical Impact Injury in Rats

Following traumatic brain injury catecholamines are routinely applied to increase cerebral perfusion. To date, it remains controversial if infusion of catecholamines is associated with diminished cerebral perfusion due to catecholamine-mediated vasoconstriction. The aims of the present study were to investigate the effects of norepinephrine and dopamine on cortical perfusion and brain edema following controlled cortical impact injury (CCII) in rats. Four hours after CCII, rats (n = 22) received either norepinephrine or dopamine with the aim of increasing MABP to 120 mm Hg for 90 minutes. Control rats were given NaCl. Cortical perfusion was measured before, during, and after catecholamine infusion using Laser Doppler flowmetry. Brain swelling was determined directly after the study period (8 hrs after CCII). Following CCII cortical perfusion was reduced by 40% compared to pre-trauma values in all rats. Parallel to the increases in MABP, cortical perfusion was significantly elevated under norepinephrine and dopamine, respectively (p < 0.05). Despite similar MABP values this increase was mostly sustained under norepinephrine. In control rats cortical perfusion remained diminished. Brain swelling was similar in all groups. Both norepinephrine and dopamine significantly increased cortical perfusion following CCII. Norepinephrine, however, was superior to dopamine in CBF. Based on increased CBF and unchanged brain swelling catecholamine-mediated vasoconstriction does not seem to occur under the present study design.

Cortical hypoperfusion precedes hyperperfusion following controlled cortical impact injury.

Impaired cerebral perfusion contributes to tissue damage following traumatic brain injury. In this longitudinal study persistence of reduced cortical perfusion employing laser doppler flowmetry was investigated following controlled cortical impact injury (CCII). Before, 30 minutes, 6, 24, and 48 hours after CCII, perfusion in pericontusional cortex was determined by moving a laser doppler probe in 50 x 0.2 mm steps over the traumatized hemisphere in 5 rats. Arterial blood gases and mean arterial blood pressure were monitored. Mean arterial blood pressure and arterial blood gases remained stable during the entire experiments. At 30 minutes and 6 hours following CCII, cortical perfusion was significantly diminished by 24% and 43% (p < 0.05), respectively compared to pre-trauma levels. At 24 and 48 hours after CCII, pericontusional blood flow was significantly increased by 64% and 123%. Cortical hypoperfusion found within the early phase following trauma is reversible and precedes a long lasting phase of hyperperfusion. Changes in tissue mediators (endothelin, acidosis, NO) could account for these findings.

Isoflurane Doubles Plasma Glutamate and Increases Posttraumatic Brain Edema

Increased plasma and cerebral glutamate levels may contribute to posttraumatic edema formation. Since volatile anesthetics elevate plasma amino acid concentrations, the influence of isoflurane on arterial plasma glutamate levels and brain edema formation was investigated in brain-injured rats. Rats were anesthetized with chloral hydrate (380 mg/kg i.p.) or isoflurane (1.2-2.0 vol%) for four hours following controlled cortical impact injury. Isoflurane significantly increased arterial glutamate levels compared to chloral hydrate (124 +/- 12 vs. 60 +/- 5 microM; p < 0.005). At eight hours after trauma, water content was significantly increased in the traumatized hemisphere compared to the non-traumatized side (p < 0.005). In addition, four hours of isoflurane anesthesia caused a significant increase in brain water content of both hemispheres compared to chloral hydrate (80.1 +/- 0.1 vs. 79.6 +/- 0.1%; p < 0.005). Prolonged isoflurane anesthesia is associated with a significant increase in arterial plasma glutamate levels and brain water content. This increase in brain water content must be considered when performing prolonged isoflurane anesthesia.

Automated Registration and Fusion of Functional and Anatomical MRI for Navigated Neurosurgery

A procedure for acquisition, automated registration and fusion of functional and anatomical magnetic resonance images (MRI) is presented and validated. The technique is based upon the acquisition of high-resolution anatomical slices at the same spatial locations as functional images (5 slices). The accuracy of registration of these slices and high-resolution 3D MRI volumes (MP-RAGE imaging) was quantified using adapted data originating from the Vanderbilt retrospective registration project (8 patients). Selecting a subset of slices from that data, the small number of images available from fMRI acquisition was taken into account. Quantitative analysis showed no loss of accuracy caused by the reduced number of slices used for registration. For real patient data, fMRI were fused with MP-RAGE images, thus integrating anatomical images with information about locations of functional areas. Via a case study, the benefits of the described approach for intraoperative navigation using an operating microscope (MKM, Zeiss) are demonstrated.

Extended Experience with Neuroendoscopic Lavage for Posthemorrhagic Hydrocephalus in Neonates

OBJECTIVEnPrevious studies have described neuroendoscopic lavage (NEL) as a procedure for the treatment of posthemorrhagic hydrocephalus in newborn infants. This report describes complications and results in an extended case series from 2 separate hospitals.nnnMETHODSnPatient records were screened for NEL procedures performed on infants with posthemorrhagic hydrocephalus between September 2010 and May 2016 (minimum follow-up period of 12 months). Efficacy of blood removal-as assessed with cerebral ultrasound, complications, eventual shunt placement rate, and subsequent shunt revisions-were recorded.nnnRESULTSnFifty-six patients (35 male) underwent NEL at a postmenstrual median age of 31 weeks and 2 days (range, 26 weeks and 1 day to 52 weeks and 3 days) and a median weight of 1523 g (range, 734-4360 g). Median follow-up was 34 months (range, 12-80). Three patients died, and 31 patients required permanent ventriculoperitoneal shunting. There was no significant correlation between the need for ventriculoperitoneal shunting and gestational age (P = 0.05), birth weight (P = 0.07), age (P = 0.17), or weight (P = 0.59) after NEL. The median number of surgical interventions per patient was 2 (range, 1-7 interventions). Revision-free shunt survival was 63.6% at 12 and 56.2% at 24 months.nnnCONCLUSIONSnNEL avoided shunt placement in 43% of newborn infants with posthemorrhagic hydrocephalus. In the shunted cohort, NEL may have also decreased the frequency of subsequent shunt revisions. The influence of NEL on neurodevelopment and safety remains to be investigated further in a multicenter setup.

Experience in shunt management on revision free survival in infants with myelomeningocele

ObjectiveDepending on the etiology of hydrocephalus in childhood, the shunt therapy still remains challenging due to frequent shunt complications leading to possible revisions such as shunt infection or shunt malfunction. In myelomeningocele (MMC) patients who often require shunt therapy, higher revisions rates were reported. In a single-center retrospective study, experiences on shunt regimen on hydrocephalus associated with MMC are presented.MethodsData of 160 infant hydrocephalus cases younger than 1xa0year of age at the time of implantation were retrospectively reviewed from the hospital database. These patients received an adjustable differential pressure valve with gravitational unit and antibiotic impregnated catheters as a primary or secondary implant during the time period of April 2007 to July 2015. The subgroup of infants cases with MMC (nu2009=u200944; age 50.6u2009±u200980.6xa0days) were compared to the remaining cohort of other hydrocephalus etiology (control group). The shunt and valve revision free survival rates were recorded until July 2017.ResultsDuring the mean follow-up of 48.7u2009±u200919.2 (7–114) months, the shunt revision free survival was 87% at 1xa0year and 49% at 60xa0months in the MMC cohort. The control group showed a shunt survival rate of 68% at 1xa0year and 39% at 60xa0months. Similarly, the valve revision free survival rate showed a significant higher rate of 92% at 1xa0year and 69% at 60xa0months in the MMC group compared to the control group (75% at 1xa0year and 51% at 60xa0months; pu2009<u20090.05). During the entire follow-up period, 37% of the MMC infants underwent a revision operation in contrast to the control group of 40%.ConclusionThe presented shunt strategy showed improved revision free survival rates in infants with a MMC-related hydrocephalus in comparison to other etiologies of hydrocephalus in infants, which might relate to infection prophylaxis and high drainage resistance integrated in the shunt system.