Influence of Blood Components on Neuroinflammation, Blood-Brain Barrier Breakdown, and Functional Damage After Acute Subdural Hematoma in Rats.

A central component of injury development after acute subdural hematoma (ASDH) is the increased intracranial pressure and consecutive mechanical reduction of cerebral blood flow (CBF). However, the role of different blood constituents in ASDH as additional lesioning factors remains unclear. This study examines the influence of blood components on neuroinflammation, blood-brain barrier (BBB) breakdown, and functional deficits in a rat model of ASDH. We infused corpuscular (whole blood, whole blood lysate, and red cell blood) and plasmatic (blood plasma, anticoagulated blood plasma, and aqueous isotonic solution) blood components into the subdural space while CBF was monitored. Rats then underwent behavioral testing. Lesion analysis and immunohistochemistry were performed 2 days after ASDH. Inflammatory reaction was assessed using staining for ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein, interleukin-1ß, tumor necrosis factor-alpha, and membrane attack complex. Integrity of the BBB was evaluated with albumin and matrix metalloproteinase 9 (MMP9) staining. We observed a significant drop in CBF in the corpuscular group (75% ± 7.5% of baseline) with distinct post-operative deficits and larger lesion volume compared to the plasmatic group (13.6 ± 5.4 vs. 1.3 ± 0.4 mm3). Further, inflammation was significantly increased in the corpuscular group with stronger immunoreaction. After whole blood infusion, albumin and MMP9 immunoreaction were significantly increased, pointing toward a disrupted BBB. The interaction between corpuscular and plasmatic blood components seems to be a key factor in the detrimental impact of ASDH. This interaction results in neuroinflammation and BBB leakage. These findings underscore the importance of performing surgery as early as possible and also provide indications for potential pharmacological targets.

Early Onset of Rapid Lesion Growth in an Acute Subdural Hematoma Model in Rats.

OBJECTIVE: Acute subdural hematoma (ASDH) leads to the highest mortality rates of all head injuries with secondary brain damage playing a pivotal role in terms of morbidity and mortality. In patients with ASDH, a delay in surgery leads to disproportional mortality. The benefit of (very) early therapy is therefore, a target of ongoing research. As the process of delayed brain damage in ASDH has not yet been described, this study therefore aimed to examine secondary lesion growth in an experimental rat model of ASDH to define the ideal timing for testing potential neuroprotective therapies. METHODS: Cerebral blood flow was monitored during ASDH induction with 300 µl of autologous blood. Lesion growth was characterized using Hematoxylin-Eosin- , Cresyl-Violet-, and Fluoro-Jade B-staining for early signs of neuronal degeneration. Histological evaluations were performed between 15 minutes and 24 hours after ASDH. RESULTS: There was a significant reduction of cerebral blood flow after ASDH. Fluoro-Jade B-positive cells were visible 15 minutes after ASDH in the lesioned hemisphere. Nonlinear growth of lesion volume from 3.7 ± 0.4 mm3 to 17.5 ± 0.6 mm3 was observed at 24 hours in Hematoxylin-Eosin-staining. CONCLUSIONS: The most damage develops between 15 minutes and 1 hour and again between 2 and 6 hours after ASDH. The time course of lesion growth supports the approach of early surgery for patients. It furthermore constitutes a basis for further ASDH research with more clearly defined time windows for therapy in animal models.

In-vivo time course of organ uptake and blood-brain-barrier permeation of poly(L-lactide) and poly(perfluorodecyl acrylate) nanoparticles with different surface properties in unharmed and brain-traumatized rats.

Background: Traumatic brain injury (TBI) has a dramatic impact on mortality and quality of life and the development of effective treatment strategies is of great socio-economic relevance. A growing interest exists in using polymeric nanoparticles (NPs) as carriers across the blood-brain barrier (BBB) for potentially effective drugs in TBI. However, the effect of NP material and type of surfactant on their distribution within organs, the amount of the administrated dose that reaches the brain parenchyma in areas with intact and opened BBB after trauma, and a possible elicited inflammatory response are still to be clarified. Methods: The organ distribution, BBB permeation and eventual inflammatory activation of polysorbate-80 (Tw80) and sodiumdodecylsulfate (SDS) stabilized poly(L-lactide) (PLLA) and poly(perfluorodecyl acrylate) (PFDL) nanoparticles were evaluated in rats after intravenous administration. The NP uptake into the brain was assessed under intact conditions and after controlled cortical impact (CCI). Results: A significantly higher NP uptake at 4 and 24 h after injection was observed in the liver and spleen, followed by the brain and kidney, with minimal concentrations in the lungs and heart for all NPs. A significant increase of NP uptake at 4 and 24 h after CCI was observed within the traumatized hemisphere, especially in the perilesional area, but NPs were still found in areas away from the injury site and the contralateral hemisphere. NPs were internalized in brain capillary endothelial cells, neurons, astrocytes, and microglia. Immunohistochemical staining against GFAP, Iba1, TNFα, and IL1ß demonstrated no glial activation or neuroinflammatory changes. Conclusions: Tw80 and SDS coated biodegradable PLLA and non-biodegradable PFDL NPs reach the brain parenchyma with and without compromised BBB by TBI, even though a high amount of NPs are retained in the liver and spleen. No inflammatory reaction is elicited by these NPs within 24 h after injection. Thus, these NPs could be considered as potentially effective carriers or markers of newly developed drugs with low or even no BBB permeation.

Multiparametric Monitoring of Early Pathophysiological Changes in a Porcine Model of Sequential Focal and Global Cerebral Ischemia.

OBJECTIVE: Large animal models of cerebral ischemia have the potential to increase the translational value of stroke research. This study aims to measure early changes of brain tissue oxygen pressure (ptiO2) and cerebral blood flow (CBF) to characterize a porcine model of sequential middle cerebral artery occlusion (MCAO) and common carotid artery occlusion (CCAO). METHODS: Eight juvenile German Landrace pigs received unilateral MCAO via a frontotemporal approach under continuous intraparenchymal multiparametric monitoring. Insufficient reduction (i.e., <50% in both ptiO2 and CBF) was followed by additional bilateral CCAO. Neurodegenerative changes were detected by Fluoro-Jade B (FJB) staining. RESULTS: Only 1 of 8 animals demonstrated a decrease of >50% in both ptiO2 and CBF after MCAO. Additional CCAO in 7 pigs led to a significant reduction of both ipsilateral and contralateral ptiO2 (P < 0.01) but not of CBF. There was no difference in ptiO2 and FJB positive area between hemispheres in this group. Measurement of ptiO2 correlated negatively with the FJB positive area (P < 0.05). CONCLUSIONS: Intraparenchymal multiparametric measurements of acute changes in ptiO2 and CBF were variable after MCAO. Bilateral CCAO led to a consistent decrease in ptiO2 and correlated with early degenerative histologic changes, but CBF did not. Real-time procedural ptiO2 monitoring could provide useful guidance in large animal ischemia models. Feasibility in the context of global cerebral hypoperfusion is demonstrated.

Does granulocyte-colony stimulating factor stimulate peripheral nerve regeneration? An experimental study on traumatic lesion of the sciatic nerve in rats.

AIM OF THE STUDY: To analyse the therapeutic potential of granulocyte-colony stimulating factor (G-CSF) treatment using a rat model of traumatic sciatic nerve lesion. CLINICAL RATIONALE FOR THE STUDY: G-CSF has proven strong neurotrophic properties in various models of ischaemic and traumatic brain injury. Fewer studies exist regarding the influence of G-CSF on posttraumatic peripheral nerve regeneration. Currently, the possibilities of pharmacological prevention or treatment of mechanical nerve injury are limited, and there is an urgent need to find new treatment strategies applicable in clinical situations. MATERIAL AND METHODS: A controlled traumatic right sciatic nerve lesion was set using a waterjet device. Three treatment groups were created. In the first group, G-CSF was administered after sciatic nerve injury. The second group received G-CSF before and after trauma, while the third group was treated with glucose 5%-solution. Sciatic nerve function was assessed clinically and electrophysiologically at day 1, and after weeks 1, 2, 4 and 6. Additionally, α-motoneurons of the spinal cord and sciatic nerve fibres were counted at week 6. RESULTS: Clinically, rats in both G-CSF groups improved faster compared to the control group. Additionally, animals treated with G-CSF had a significantly better improvement of motor potential amplitude and motor nerve conduction velocity at week 6 (p < 0.05). Histologically, G-CSF treatment resulted in a significantly higher number of α-motoneurons and small myelinated nerve fibres compared to placebo treatment (p < 0.05). CONCLUSIONS AND CLINICAL IMPLICATIONS: Under G-CSF treatment, the recovery of motor nerve conduction velocity and amplitude was enhanced. Further, signs of nerve regeneration and preservation of α-motoneurons were observed. These results indicate that G-CSF might accelerate and intensify the recovery of injured nerves. Thus, treatment with G-CSF may be beneficial for patients with peripheral nerve damage, and should be explored in further clinical studies.

Is a Mask That Covers the Mouth and Nose Free from Undesirable Side Effects in Everyday Use and Free of Potential Hazards?

Many countries introduced the requirement to wear masks in public spaces for containing SARS-CoV-2 making it commonplace in 2020. Up until now, there has been no comprehensive investigation as to the adverse health effects masks can cause. The aim was to find, test, evaluate and compile scientifically proven related side effects of wearing masks. For a quantitative evaluation, 44 mostly experimental studies were referenced, and for a substantive evaluation, 65 publications were found. The literature revealed relevant adverse effects of masks in numerous disciplines. In this paper, we refer to the psychological and physical deterioration as well as multiple symptoms described because of their consistent, recurrent and uniform presentation from different disciplines as a Mask-Induced Exhaustion Syndrome (MIES). We objectified evaluation evidenced changes in respiratory physiology of mask wearers with significant correlation of O2 drop and fatigue (p < 0.05), a clustered co-occurrence of respiratory impairment and O2 drop (67%), N95 mask and CO2 rise (82%), N95 mask and O2 drop (72%), N95 mask and headache (60%), respiratory impairment and temperature rise (88%), but also temperature rise and moisture (100%) under the masks. Extended mask-wearing by the general population could lead to relevant effects and consequences in many medical fields.

Implantable Sensors Based on Gold Nanoparticles for Continuous Long-Term Concentration Monitoring in the Body.

Implantable sensors continuously transmit information on vital values or biomarker concentrations in bodily fluids, enabling physicians to survey disease progression and monitor therapeutic success. However, currently available technologies still face difficulties with long-term operation and transferability to different analytes. We show the potential of a generalizable platform based on gold nanoparticles embedded in a hydrogel for long-term implanted biosensing. Using optical imaging and an intelligent sensor/reference-design, we assess the tissue concentration of kanamycin in anesthetized rats by interrogating our implanted sensor noninvasively through the skin. Combining a tissue-integrating matrix, robust aptamer receptors, and photostable gold nanoparticles, our technology has strong potential to extend the lifetime of implanted sensors. Because of the easy adaptability of gold nanoparticles toward different analytes, our concept will find versatile applications in personalized medicine or pharmaceutical development.

Intrahematomal Ultrasound Enhances RtPA-Fibrinolysis in a Porcine Model of Intracerebral Hemorrhage.

Catheter-based ultrasound-thrombolysis has been successfully used in a small clinical trial in order to enhance recombinant tissue plasminogen activator (rtPA)-fibrinolysis, for the treatment of spontaneous intracerebral hemorrhages (ICHs). The aim of this study was to investigate the ultra-early effects of ultrasound on hematoma and the surrounding brain tissue in a porcine ICH-model. To achieve this, 21 pigs with a right frontal ICH were randomly assigned to four groups: (1) drainage (n = 3), (2) drainage + rtPA (n = 6), (3) drainage + ultrasound (n = 6), and (4) drainage + ultrasound + rtPA (n = 6). The hematoma volume assessment was performed using cranial MRI before and after the treatments. Subsequently, the brain sections were analyzed using HE-staining and immunohistochemistry. The combined treatment using rtPA and ultrasound led to a significantly higher hematoma reduction (62 ± 5%) compared to the other groups (Group 1: 2 ± 1%; Group 2: 30 ± 12%; Group 3: 18 ± 8% (p < 0.0001)). In all groups, the MRI revealed an increase in diffusion restriction but neither hyper- or hypoperfusion, nor perihematomal edema. HE stains showed perihematomal microhemorrhages were equally distributed in each group, while edema was more pronounced within the control group. Immunohistochemistry did not reveal any ultra-early side effects. The combined therapy of drainage, rtPA and ultrasound is a safe and effective technique for hematoma-reduction and protection of the perihematomal tissue in regard to ultra-early effects.

Systematic Analysis of Combined Thrombolysis Using Ultrasound and Different Fibrinolytic Drugs in an in Vitro Clot Model of Intracerebral Hemorrhage.

Adequate removal of blood clots by minimally invasive surgery seems to correlate with a better clinical outcome in patients with intracerebral hemorrhages (ICHs). Moreover, neurotoxic effects of recombinant tissue plasminogen activator have been reported. The aim of this study was to improve fibrinolysis using an intra-clot ultrasound application with tenecteplase and urokinase in our established ICH clot model. One hundred thirty clots were produced from 25 or 50 mL of human blood, incubated for different periods and equipped with drainage, through which an ultrasound catheter was placed in 65 treatment clots for 1 h, randomly allocated into three groups: administration of ultrasound, administration of 60 IU of tenecteplase or administration of 30,000 IU urokinase. Relative end weights were compared. This study found a significant increase in thrombolysis caused by a combination of ultrasound and fibrinolytic drugs, whereas ultrasound and tenecteplase are significantly more effective in the treatment of larger and aged clots.

Comparative analysis of fibrinolytic properties of Alteplase, Tenecteplase and Urokinase in an in vitro clot model of intracerebral haemorrhage.

OBJECTIVE: Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral and intraventricular haemorrhage (ICH and IVH). However, the MISTIE III and CLEAR III trial failed to show significant improvement of favourable outcomes. Besides experimental and clinical trials revealed neurotoxic effects of rtPA. The demand for optimization of fibrinolytic therapy persists. Herein, we used our recently devised clot model of ICH to systematically analyse fibrinolytic properties of rtPA, tenecteplase and urokinase. METHODS: In vitro clots of human blood (size: 25 ml and 50 ml; age: 1.5 tenecteplase, 24 tenecteplase and 48 tenecteplase) were produced and equipped with a catheter into the clot core for drug delivery and drainage. Various doses of tenecteplase and urokinase with different treatment periods were examined (overall 117 clots), assessing the optimal dose and treatment time of these fibrinolytics. Clots were weighed before and at the end of treatment. These results were compared with clots treated with 1 mg rtPA or with 0.9% sodium chloride solution. RESULTS: The optimal treatment scheme of tenecteplase was found to be 100 IU with an incubation time of 30 min, for urokinase it was 50 000 IU with an incubation time of 20 min. The relative clot end weight of tenecteplase and urokinase (31.3±11.9%, 34.8 ±7.7%) was comparable to rtPA (36.7±10.7%). Larger clots were more effectively treated with tenecteplase compared to the control group (P=0.0013). urokinase and tenecteplase had similar lysis rates in aged clots and 90 min clots. One and two repetitive treatments with tenecteplase were as effective as two and three cycles of urokinase. CONCLUSIONS: In our in vitro clot model we could determine optimal treatment regimens of tenecteplase (100 IU, 30 min) and urokinase (50 000 IU, 20 min). Urokinase and tenecteplase were comparable in their fibrinolytic potential compared to 1mg rtPA in small clots and showed an effective lysis in aged clots. tenecteplase was more effective in larger clots.

Real-Time Overlapping of Indocyanine Green-Video Angiography With White Light Imaging for Vascular Neurosurgery: Technique, Implementation, and Clinical Experience.

BACKGROUND: Fluorescent-guided techniques in vascular neurosurgery can be demonstrated via black and white indocyanine green videoangiography (ICG-VA). Multispectral imaging (MFL) is a new method, which overlaps fluorescence with the white light and provides a fluorescent white light augmented reality image to the surgeon. OBJECTIVE: To investigate (a) whether MFL can enhance the visualization of the blood-flow with simultaneous visualization of the anatomic structures and (b) if MFL can ergonomically improve the microvascular surgical treatment compared to ICG-VA. METHODS: A digital imaging of the blood flow after intravenous injection of ICG on 7 pigs was performed in real time under white light, standard fluorescence, and MFL. The blood flow was interrupted with a surgical clip, demonstrating the blockage of the blood flow. We prospectively included 30 patients with vascular deformities. The vasculature was visualized on the microscope's monitor and through the microscope's eyepiece. RESULTS: In the animal experiment, the visualization of the anatomy and the blood flow under MFL produced high resolution images. The occlusion of blood vessels demonstrated sufficiently the blockage of tissue perfusion and its reperfusion after clip removal. During all 30 surgical cases, the MFL technique and the direct delivery of the pseudo-colored image through the eyepiece allowed for enhanced anatomic and dynamic data. CONCLUSION: MFL was shown to be superior to the classic ICG-VA, delivering enhanced data and notably improving the workflow due to the simultaneous and precise white light visualization of the blood flow and the surrounding anatomic structures.

In vitro testing of a funnel-shaped tip catheter model to decrease clot migration during mechanical thrombectomy.

One limitation of mechanical thrombectomy (MT) is clot migration during procedure. This might be caused by abruption of the trapped thrombus at the distal access catheter (DAC) tip during stent-retriever retraction due to the cylindrical shaped tip of the DAC. Aiming to solve this problem, this study evaluates the proof-of-concept of a new designed funnel-shaped tip, in an experimental in vitro setting. Two catheter models, one with a funnel-shaped tip and one with a cylindrical-shaped tip, were compared in an experimental setup. For MT a self-made vessel model and thrombi generated from pig's blood were used. MT was performed 20 times for each device using two different stent-retrievers, 10 times respectively. For the funnel-shaped model: for both stent-retrievers (Trevo XP ProVue 3/20 mm; Trevo XP ProVue 4/20 mm) MT was successful at first pass in 9/10 (90%), respectively. For the cylindrical-shaped model: MT was successful at first pass in 5/10 (50%) with the smaller stent-retriever and in 6/10 (60%) with the larger stent-retriever. The experiments show a better recanalization rate for funnel-shaped tips, than for cylindrical-shaped tips. These results are indicating a good feasibility for this new approach, thus the development of a prototype catheter seems reasonable.

The Cerebral Thrombin System Is Activated after Intracerebral Hemorrhage and Contributes to Secondary Lesion Growth and Poor Neurological Outcome in C57Bl/6 Mice.

With increasing evidence for the existence of a cerebral thrombin system, coagulation factor IIa (thrombin) is suspected to influence the pathogenesis of secondary injury progression after intracerebral hemorrhage (ICH). We hypothesized that mechanisms associated with local volume expansion after ICH, rather than blood constituents, activate the cerebral thrombin system and are responsible for detrimental neurological outcome. To test this hypothesis, we examine the local thrombin expression after ICH in a C57BL/6N mouse model in the presence and absence of blood constituents. ICH was established using stereotaxic orthotopic injection of utologous blood (n = 10) or silicone oil as inert volume substance (n = 10) into the striatum. Intracranial pressure (ICP), cerebral blood flow (CBF), and mean arterial blood pressure (MAP) were monitored during and 30 min after the procedure. No significant differences between ICP, CBF, and MAP were found between both groups. Prothrombin messenger RNA expression was upregulated early after ICH. Immunohistochemistry showed an increase of perilesional thrombin in both groups (blood, 4.24-fold; silicone, 3.10-fold), whereas prothrombin fragment (F1.2) was elevated only in the absence of whole blood. Thrombin expression is colocalized with neuronal antigen expression. After 24 h, lesion size and neuronal loss were similar. Perihematomal thrombin correlated with increased neuronal loss and detrimental neurological outcome in vivo. In our study, we demonstrate, for the first time, that the local cerebral thrombin system is activated after ICH and that this activation is independent of the presence of whole-blood constituents. In our study, neuronal damage is driven by local thrombin expression and leads to an adverse clinical outcome.

Esophageal Blood Flow May Not Be Directly Influenced by Anastomotic Tension: An Exploratory Laser Doppler Study in Swine.

BACKGROUND: Anastomotic tension has been linked to leakage and stenosis in esophageal surgery in both adults and children. We aimed to determine the effects of esophageal topography, operative technique, and anastomotic tension on esophageal blood flow. MATERIALS AND METHODS: We divided and reanastomosed the esophagi at the carinal level with increasing levels of anastomotic tension in piglets (n = 10) and sham controls (n = 4). We examined esophageal blood flow pre- and postoperatively using laser Doppler flowmetry at the anastomosis and two predetermined proximal and distal points. Blood flow in relation to distance from the anastomosis was examined by multivariate linear regression. RESULTS: Thoracotomy alone did not influence perfusion at the carinal level in shams (Δ = 3.13 laser Doppler units, 95% confidence interval: -3.4 to 9.7, p = 0.2686). We constructed a (F[5,134] = 6.34, p < 0.0001) multinomial regression model based on distance to the anastomotic site and pre-/postoperative measurements (adjusted R 2 = 0.1624). Tissue blood flow was higher distant to the carina, but lower postoperatively and not influenced by the tension resulting from the extent of resection (F[1, 8] = 1.134, p = 0.318). CONCLUSION: Esophageal blood flow is higher at greater distances to the carinal level and hampered by esophageal division and reanastomosis. The extent of resection has less influence than previously assumed. Therefore, leakage and stenosis after esophageal anastomosis may not solely be caused by insufficient anastomotic blood flow.

Doppler sonography enhances rtPA-induced fibrinolysis in an in vitro clot model of spontaneous intracerebral hemorrhages.

BACKGROUND: Transcranial Doppler (TCD) was shown to enhance intravascular fibrinolysis by rtPA in ischemic stroke. Studies revealed that catheter-based administration of rtPA induces lysis of intracerebral hemorrhages (ICH). However, it is unknown whether TCD would be suitable to enhance rtPA-induced fibrinolysis in patients with ICH. The aim of this study was to assess the potential of TCD to enhance rtPA-induced fibrinolysis in an in vitro clot system. METHODS: Reproducible human blood clots of 25 ml were incubated in a water bath at 37°C during treatments. They were weighed before and after 6 different treatments: (I) control (incubation only), (II) rtPA only, (III) one Doppler probe, (IV) two Doppler probes placed vis-à-vis, (V) one probe and rtPA and (VI) two probes and rtPA. To quantify lysis of the blood clots and attenuation of the Doppler through a temporal squama acoustic peak rarefaction pressure (APRP) was measured in the field of the probes. Temperature was assessed to evaluate possible side effects. RESULTS: Clot weight was reduced in all groups. The control group had the highest relative end weight of 70.2%±7.2% compared to all other groups (p<0,0001). Most efficient lysis was achieved using (VI) 2 probes and rtPA 36.3%±4.4% compared to (II, III, IV) (p<0.0001; p = 0.0002; p = 0.048). APRP was above lysis threshold (535.5±7.2 kPa) using 2 probes even through the temporal squama (731.6±32.5 kPa) (p = 0.0043). There was a maximal temperature elevation of 0.17±0.07°C using both probes. CONCLUSIONS: TCD significantly enhances rtPA-induced lysis of blood clots, and the effect is amplified by using multiple probes. Our results indicate that bitemporal TCD insonation of hematomas could be a new and safe approach to enhance fibrinolysis of ICH´s treated with intralesional catheter and rtPA.

Occurrence of Spontaneous Cortical Spreading Depression Is Increased by Blood Constituents and Impairs Neurological Recovery after Subdural Hematoma in Rats.

Acute subdural hemorrhage (ASDH) is common and associated with severe morbidity and mortality. To date, the role of spontaneous cortical spreading depression (sCSD) in exaggerating secondary injury after ASDH, is poorly understood. The present study contains two experimental groups: First, we investigated and characterized the occurrence of sCSD after subdural blood infusion (300 µL) via tissue impedance (IMP) measurement in a rat model. Second, we compared the occurrence and influence of sCSD on lesion growth and neurological deficit in the presence and absence of whole blood constituents. In the first experimental group, three IMP traits could be distinguished after ASDH: no sCSD, recurrent sCSD, and constant elevated IMP (anoxic depolarization [AD]). In the second experimental group, sCSD occurred more often after autologous blood, compared with paraffin oil infusion. Lesion volume 7 days post-ASDH was 27.3 ± 6.8 mm3 after blood and 3.4 ± 2.1 mm3 after paraffin oil infusion. Subgroup analysis showed larger lesion size in animals with sCSD, than in those without. Further, occurrence of sCSD led to worse neurological outcomes in both groups. sCSD occurs early after ASDH and does not depend on the presence of whole blood constituents. However, numbers and degree of sCSD are more frequent and severe after autologous blood infusion, compared with an inert volume substance. The occurrence of sCSD leads to lesion growth and worse neurological outcome. Thus, our data advocate close monitoring and targeted treatment of sCSD after ASDH evacuation.

Thrombin contributes to the injury development and neurological deficit after acute subdural hemorrhage in rats only in collaboration with additional blood-derived factors.

BACKGROUND: Acute subdural hemorrhage (ASDH) is a severe consequence of traumatic brain injury. The occurrence of subdural blood increases the lethality of these patients independent of the amount of blood or elevated intracranial pressure. Thrombin is one of the potential harmful blood components. Possible harmful effects of thrombin are mediated via the Protease-activated-receptor-1 (PAR1) and thus, translating the acute Thrombin release after ASDH into cell loss. The objectives of the present study were twofold, namely to examine (1) the impact of direct thrombin inhibition in the acute phase after hemorrhage on the long-term histological and functional deficits and (2) the early inhibition of PAR1 activation by thrombin with the selective antagonist SCH79797 on lesion volume at 14 days after ASDH. The effects of thrombin on the lesion size were investigated in two separate experiments via (1) direct thrombin inhibition in the subdural infused blood (Argatroban 600 µg) as well as by (2) intraventricular injection of the PAR-1 antagonist SCH79797 (1 µg or 5 µg). Lesion volume and behavior deficits using a neurological deficit score and a motor function test (beam balance test) were analyzed as outcome parameters at 14 days after injury. RESULTS: 59 Male Sprague-Dawley rats received a subdural infusion of 300 µl autologous blood or sham operation. Lesion volume at 14 days after ASDH tended to be smaller in the Argatroban-treated group when compared to the vehicle group (8.1 ± 1.1 vs. 10.1 ± 2.3 mm2, n.s.). Motor deficits in the beam balance test were not significantly less severe in the Argatroban-treated group. Animals treated with SCH79797 also showed a trend towards dose-dependent decreased lesion volume in comparison to the vehicle-treated group (1 µg: 4.3 ± 0.7 mm3; 5 µg: 3.8 ± 1.1 mm3; vehicle: 6.5 ± 2.0 mm3, n.s). CONCLUSIONS: Thrombin inhibition in the subdural blood and local cerebral blockade of PAR-1 cause a tendency towards reduced lesion volume or functional recovery. All results show a trend in favor of the acute treatment on the outcome parameters. Our results suggests that thrombin could be an important blood-derived factor during acute subdural hemorrhage that translates its deleterious effects in concert with other blood-induced factors.

Accelerometer-Based Assessment of Intestinal Peristalsis: Toward Miniaturized Low-Power Solutions for Intestinal Implants.

Intestinal electrical stimulation via implants is already used to treat several disorders like constipation or incontinence. Stimulation parameters are most often empiric and not based on systematic studies. One prerequisite to evaluate effects of intestinal electrical stimulation is a direct assessment of intestinal motility. Some common methods are strain gauge transducers or manometry. With both the methods, it is not possible to record the exact 3-D movement. Therefore, we established a new method to record gastrointestinal motility with ultraminiaturized accelerometers, directly glued to the outer surface of the stomach, small intestine, and colon. With this technique, we were able to record precise local motility changes after electrical stimulation. Due to the low energy demand and the small size of the system, it is potentially useful for chronic measurements at multiple sites of the intestinal tract. We will present our first results regarding stimulation-dependent motility changes using up to eight implanted accelerometers in an acute pig model.