Mild Hypothermia via External Cooling Improves Lung Function and Alleviates Pulmonary Inflammatory Response and Damage in Two-Hit Rabbit Model of Acute Lung Injury.

OBJECTIVES: Targeted temperature management (TTM) with therapeutic hypothermia (TH) has an organ-protective effect by mainly reducing inflammatory response. Here, our objective was to determine, for the first time, whether mild TH with external cooling, a simple and inexpensive method, could be safe or even beneficial in two-hit rabbit model of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). METHODS: Twenty-two New Zealand rabbits (6-month-old) were randomly divided into healthy control (HC) with conventional ventilation, but without injury, model group (ALI), and hypothermia group with external cooling (ALI-HT). After induction of ALI/ARDS through mild lung-lavages followed by non-protective ventilation, mild hypothermia was started in ALI-HT group (body temperature of 33-34 °C). All rabbits were conventionally ventilated for an additional 6-h by recording respiratory parameters. Finally, lung histopathology and inflammatory response were evaluated. RESULTS: Hypothermia was associated with higher oxygen saturation, resulting in partial improvement in the P/F ratio (PaO2/FiO2), oxygenation index, mean airway pressure, and PaCO2, but did not affect lactate levels. The ALI-HT group had lower histopathological injury scores (hyperemia, edema, emphysema, atelectasis, and PMN infiltration). Further, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and -8 levels in lung tissue and serum samples markedly reduced due to hypothermia. CONCLUSION: Mild TH with external cooling reduced lung inflammation and damage, whereas it resulted in partial improvement in gas exchanges. Our findings highlight that body temperature control may be a potentially supportive therapeutic option for regulating cytokine production and respiratory parameters in ALI/ARDS.

Continuous Endotracheal Tube Cuff Pressure Control Decreases Incidence of Ventilator-Associated Pneumonia in Patients with Traumatic Brain Injury.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a common cause of morbidity and mortality in intensive care unit (ICU), and among the several preventative strategies described to reduce the incidence of VAP, the most important is the endotracheal tube cuff (ETC) pressure. The present study was conducted on 60 patients who required mechanical ventilation (MV) in the ICU with traumatic brain injury (TBI). METHODS: The patients were randomized into two groups of 30, in which ETC pressure was regulated using a smart cuff manager (SCM) (Group II), or manual measurement approach (MMA) (Group I). Demographic data, MV duration, length of ICU stay and mortality rates were recorded. The clinical pulmonary infection scores (CPISs), C-reactive protein (CRP) values, and the fraction of inspired oxygen (FiO2) and positive end-expiratory pressure (PEEP) values of the groups were compared at baseline, and at hours 48, 72 and 96. RESULTS: In Group I, CPIS values significantly higher than Group II in 48th, 72nd and 96th hours (p < 0.05). In Group I, PEEP values and deep tracheal aspirate (DTA) culture growth rates significantly higher than Group II in 72nd and 96th hours (p < 0.05). CONCLUSION: The continuous maintenance of ETC pressure using SCM reduced the incidence of VAP.

Intranasal levosimendan prevents cognitive dysfunction and apoptotic response induced by repeated isoflurane exposure in newborn rats.

Anesthetic-induced toxicity in early life may lead to risk of cognitive decline at later ages. Notably, multiple exposures to isoflurane (ISO) cause acute apoptotic cell death in the developing brain and long-term cognitive dysfunction. This study is the first to investigate whether levosimendan (LVS), known for its protective myocardial properties, can prevent anesthesia-induced apoptotic response in brain cells and learning and memory impairment. Postnatal day (P)7 Wistar albino pups were randomly assigned to groups consisting of an equal number of males and females in this laboratory investigation. We treated rats with LVS (0.8 mg/kg/day) intranasally 30 min before each ISO exposure (1.5%, 3 h) at P7+9+11. We selected DMSO as the drug vehicle. Also, the control group at P7+9+11 received 50% O2 for 3 h instead of ISO. Neuroprotective activity of LVS against ISO-induced cognitive dysfunction was evaluated by Morris water maze. Expression of apoptotic-related proteins was detected in the whole brain using western blot. LVS pretreatment significantly prevented anesthesia-induced deficit in spatial learning (at P28-32) and memory (at P33, P60, and P90). No sex-dependent difference occurred on any day of the training and probe trial. Intranasal LVS was also found to significantly prevent the ISO-induced apoptosis by reducing Bax and cleaved caspase-3, and by increasing Bcl-2 and Bcl-xL. Our findings support pretreatment with intranasal LVS application as a simple strategy in daily clinical practice in pediatric anesthesia to protect infants and children from the risk of general anesthesia-induced cell death and cognitive declines.

Effect of Isoflurane Exposure with Administration of Polyunsaturated Fatty Acids on Cognition in Developing Rats.

OBJECTIVE: The developing brain is vulnerable to the negative effects of anaesthetics. We aimed to investigate the effect of isoflurane and polyunsaturated fatty acids (PUFAs) on cognition. METHODS: A total of 64, ten days old rats were randomly divided into 4 groups: group O2 (oxygen group), group Iso (isoflurane group), group Iso-S (isoflurane+saline) and group Iso-PUFAs (isoflurane+intraperitoneal [IP] PUFAs emulsion). Rats in groups Iso, Iso-S and Iso-PUFAs were exposed to 1.5% isoflurane in 50% oxygen for 6 hours. Rats in group O2 breathed only 50% oxygen. Before anaesthesia, rats in group Iso-S were administered 0.5 mL isotonic and rats in group Iso-PUFAs were administered 5 mL kg-1 PUFAs emulsion by IP injection. The Morris water maze (MWM) test was performed on postnatal 28-33 days. Histological evaluation and immune histochemical staining (Bcl-2 antibody) were performed on postnatal day 11 on rat brains. RESULTS: As demonstrated by the reduction in the escape latency on days 3, 4 and 5 compared with day 1, all rats learned the task during the acquisition period. In contrast to others, rats in group Iso spent significantly lower time to find the platform on day 2 than on day 1 (p=0.034). No significant difference was found among the groups in terms of time spent in finding the platform. There were no significant differences in probe trials, histological features and Bcl-2 immunoreactivity among the groups. CONCLUSION: Isoflurane did not cause cognitive dysfunction and neuronal death, and a single dose of PUFAs emulsion had no effect on cognition either.

Isoflurane exposure in infant rats acutely increases aquaporin 4 and does not cause neurocognitive impairment.

Isoflurane is commonly used in pediatric population, but its mechanism of action in cognition is unclear. Aquaporin 4 (AQP4) regulates water content in blood, brain, and cerebrospinal fluid. Various studies have provided evidence for the role of AQP4 in synaptic plasticity and neurocognition. In this study, we aimed to determine whether a prolonged exposure to isoflurane in infant rats is associated with cognition and what effect this exposure has on AQP4 expression. Ten-day-old [postnatal day (P) 10] Wistar albino rats were randomly allocated to isoflurane group (n = 32; 1.5% isoflurane in 50% oxygen for 6 hours) or control group (n = 32; only 50% oxygen for 6 hours). Acute (P11) and long-term (P33) effects of 6-hour anesthetic isoflurane exposure on AQP4 expression were analyzed in whole brains of P11 and P33 rats by RT-qPCR and Western blot. Spatial learning and memory were assessed on P28 to P33 days by Morris Water Maze (MWM) test. The analysis revealed that isoflurane increased acutely both mRNA (~4.5 fold) and protein (~90%) levels of AQP4 in P11 rats compared with control group. The increasing levels of AQP4 in P11 were not observed in P33 rats. Also, no statistically significant change between isoflurane and control groups was observed in the latency to find the platform during MWM training and probe trial. Our results indicate that a single exposure to isoflurane anesthesia does not influence cognition in infant rats. In this case, acutely increased AQP4 after isoflurane anesthesia may have a protective role in neurocognition.

Neurotrophin-3 provides neuroprotection via TrkC receptor dependent pErk5 activation in a rat surgical brain injury model.

BACKGROUND: Surgical brain injury (SBI) which occurs due to the inadvertent injury inflicted to surrounding brain tissue during neurosurgical procedures can potentiate blood brain barrier (BBB) permeability, brain edema and neurological deficits. This study investigated the role of neurotrophin 3 (NT-3) and tropomyosin related kinase receptor C (TrkC) against brain edema and neurological deficits in a rat SBI model. METHODS: SBI was induced in male Sprague Dawley rats by partial right frontal lobe resection. Temporal expression of endogenous NT-3 and TrkC was evaluated at 6, 12, 24 and 72 h after SBI. SBI rats received recombinant NT-3 which was directly applied to the brain surgical injury site using gelfoam. Brain edema and neurological function was evaluated at 24 and 72 h after SBI. Small interfering RNA (siRNA) for TrkC and Rap1 was administered via intracerebroventricular injection 24 h before SBI. BBB permeability assay and western blot was performed at 24 h after SBI. RESULTS: Endogenous NT-3 was decreased and TrkC expression increased after SBI. Topical administration of recombinant NT-3 reduced brain edema, BBB permeability and improved neurological function after SBI. Recombinant NT-3 administration increased the expression of phosphorylated Rap1 and Erk5. The protective effect of NT-3 was reversed with TrkC siRNA but not Rap1 siRNA. CONCLUSIONS: Topical application of NT-3 reduced brain edema, BBB permeability and improved neurological function after SBI. The protective effect of NT-3 was possibly mediated via TrkC dependent activation of Erk5.

Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage is the most devastating stroke subtype with high rates of mortality and morbidity. Furthermore, no clinically approved treatment exists that effectively increases survival or improves quality of life for survivors. Effective modeling is necessary to elucidate the pathophysiological mechanisms of intracerebral hemorrhage and evaluate potential therapeutic approaches. Rodent models are most utilized because of their cost-effectiveness, and because rodent brain development and structures are well documented. Herein, we describe two intracerebral hemorrhage mouse models: the autologous blood double-injection and collagenase infusion models.

Multiple mechanisms underlying neuroprotection by secretory phospholipase A2 preconditioning in a surgically induced brain injury rat model.

BACKGROUND: Intra-operative bleeding, post-operative brain edema and neuroinflammation are major complications in patients with surgical brain injury (SBI). Phospholipase A2 (PLA2) is the upstream enzyme which initiates the PLA2, 5-lipoxygenase (5-LOX) and leukotriene B4 (LTB4) inflammatory pathway. We hypothesized PLA2preconditioning (PPC) prior to SBI can activate endogenous anti-inflammatory responses to protect against SBI. This study evaluated if PPC can ameliorate neurosurgical complications and elucidated PPC-mediated possible protective mechanisms in a rat SBI model. METHODS: Total 105 adult male Sprague Dawley rats were used for this study. SBI was induced by partial resection of the right frontal lobe. PLA2 or 0.9% NaCl was injected via rats' tail vein for 3 consecutive days prior to SBI. For mechanism study, a selective PLA2 inhibitor, Manoalide and 5-LOX inhibitor, Zileuton were injected intravenously with PPC to elucidate the role of PLA2 and 5-LOX in PPC-mediated anti-inflammatory effects. Brain water content (BWC) and lung water content, neurological tests, ELISA, western blot, immunohistochemistry, white blood cells (WBC) count, and spectrophotometric assay for intra-operative hemorrhage volume were evaluated. RESULTS: First, PPC reduced brain water content, intra-operative bleeding, and improved neurological function after SBI. Second, PPC decreased 5-LOX expression and brain leukocyte infiltration, while increasing glial fibrillary acidic protein (GFAP) expression in the peri-resection brain tissue after SBI. Third, PPC induced peripheral inflammation represented by mild pulmonary inflammation and increased peripheral blood WBC count and LTB4 level. Lastly, PPC increased blood glucose concentration and glucocorticoid levels after SBI. In addition, PPC mediated above-mentioned changes were partially reversed by administration of PLA2 inhibitor, Manoalide and 5-LOX inhibitor, Zileuton. CONCLUSIONS: PPC conferred neuroprotection against SBI via multi-target involvement induced anti-inflammatory mechanisms.

Autophagy after Subarachnoid Hemorrhage: Can Cell Death be Good?

BACKGROUND: Autophagy is a prosurvival, reparative process that maintainsww cellular homeostasis through lysosomal degradation of selected cytoplasmic components and programmed death of old, dysfunctional, or unnecessary cytoplasmic entities. According to growing evidence, autophagy shows beneficial effects following subarachnoid hemorrhage (SAH). SAH is considered one of the most devastating forms of stroke. METHODS: In this review lies in revealing the pathophysiological pathways and the effects of autophagy. Current results from animal studies will be discussed focusing on the effects of inhibitors and inducers of autophagy. In addition, this review discusses the clinical translation of potential neuropharmacological targets that can help prevent early brain injury (EBI) following SAH by incorporating programmed cell death into clinical management. RESULTS: Published data showed that autophagy mechanisms have a prosurvival effect to reduce apoptotic cell death after SAH. However, if SAH exceeds a certain stress threshold, autophagy mechanisms lead to increased apoptotic cell death, more brain injury, and worse outcome. CONCLUSION: Future investigation on the differences and molecular switches between protective mechanisms of autophagy and excessive "self-eating" autophagy leading to cell death is needed to achieve more insight into the complex pathophysiology of brain injury after SAH. If autophagy after SAH can be controlled to lead to beneficial effects only, as the physiological self-control mechanism, this could be an important target for treatment.

A Look into Stem Cell Therapy: Exploring the Options for Treatment of Ischemic Stroke.

Neural stem cells (NSCs) offer a potential therapeutic benefit in the recovery from ischemic stroke. Understanding the role of endogenous neural stem and progenitor cells under normal physiological conditions aids in analyzing their effects after ischemic injury, including their impact on functional recovery and neurogenesis at the site of injury. Recent animal studies have utilized unique subsets of exogenous and endogenous stem cells as well as preconditioning with pharmacologic agents to better understand the best situation for stem cell proliferation, migration, and differentiation. These stem cell therapies provide a promising effect on stimulation of endogenous neurogenesis, neuroprotection, anti-inflammatory effects, and improved cell survival rates. Clinical trials performed using various stem cell types show promising results to their safety and effectiveness on reducing the effects of ischemic stroke in humans. Another important aspect of stem cell therapy discussed in this review is tracking endogenous and exogenous NSCs with magnetic resonance imaging. This review explores the pathophysiology of NSCs on ischemic stroke, stem cell therapy studies and their effects on neurogenesis, the most recent clinical trials, and techniques to track and monitor the progress of endogenous and exogenous stem cells.

IVIG activates FcγRIIB-SHIP1-PIP3 Pathway to stabilize mast cells and suppress inflammation after ICH in mice.

Following intracerebral hemorrhage (ICH), the activation of mast cell contributes to brain inflammation and brain injury. The mast cell activation is negatively regulated by an inhibitory IgG-receptor. It's signals are mediated by SHIP (Src homology 2-containing inositol 5' phosphatase), in particular SHIP1, which activation leads to hydrolyzation of PIP3 (Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3, leading to the inhibition of calcium mobilization and to the attenuation of mast cell activation. Intravenous immunoglobulin (IVIG) is a FDA-approved drug containing IgG. We hypothesized that IVIG will attenuate the ICH-induced mast cell activation via FcγRIIB/SHIP1 pathway, resulting in a decrease of brain inflammation, protection of the blood-brain-barrier, and improvement of neurological functions after ICH. To prove this hypothesis we employed the ICH collagenase mouse model. We demonstrated that while ICH induced mast cell activation/degranulation, IVIG attenuated post-ICH mast cell activation. Mast cell deactivation resulted in reduced inflammation, consequently attenuating brain edema and improving of neurological functions after ICH. Furthermore using siRNA-induced in vivo knockdown approach we demonstrated that beneficial effects of IVIG were mediated, at least partly, via SHIP1/PIP3 pathway. We conclude that IVIG treatment represents a promising therapeutic approach potentially able to decrease mortality and morbidity after ICH in experimental models.

Naja sputatrix Venom Preconditioning Attenuates Neuroinflammation in a Rat Model of Surgical Brain Injury via PLA2/5-LOX/LTB4 Cascade Activation.

Inflammatory preconditioning is a mechanism in which exposure to small doses of inflammatory stimuli prepares the body against future massive insult by activating endogenous protective responses. Phospholipase A2/5-lipoxygenase/leukotriene-B4 (PLA2/5-LOX/LTB4) axis is an important inflammatory signaling pathway. Naja sputatrix (Malayan spitting cobra) venom contains 15% secretory PLA2 of its dry weight. We investigated if Naja sputatrix venom preconditioning (VPC) reduces surgical brain injury (SBI)-induced neuroinflammation via activating PLA2/5-LOX/LTB4 cascade using a partial frontal lobe resection SBI rat model. Naja sputatrix venom sublethal dose was injected subcutaneously for 3 consecutive days prior to SBI. We observed that VPC reduced brain edema and improved neurological function 24 h and 72 h after SBI. The expression of pro-inflammatory mediators in peri-resection brain tissue was reduced with VPC. Administration of Manoalide, a PLA2 inhibitor or Zileuton, a 5-LOX inhibitor with VPC reversed the protective effects of VPC against neuroinflammation. The current VPC regime induced local skin inflammatory reaction limited to subcutaneous injection site and elicited no other toxic effects. Our findings suggest that VPC reduces neuroinflammation and improves outcomes after SBI by activating PLA2/5-LOX/LTB4 cascade. VPC may be beneficial to reduce post-operative neuroinflammatory complications after brain surgeries.

Recombinant Slit2 Reduces Surgical Brain Injury Induced Blood Brain Barrier Disruption via Robo4 Dependent Rac1 Activation in a Rodent Model.

Brain tissue surrounding surgical resection site can be injured inadvertently due to procedures such as incision, retractor stretch, and electrocauterization when performing neurosurgical procedures, which is termed as surgical brain injury (SBI). Blood brain barrier (BBB) disruption due to SBI can exacerbate brain edema in the post-operative period. Previous studies showed that Slit2 exhibited vascular anti-permeability effects outside the brain. However, BBB protective effects of Slit2 following SBI has not been evaluated. The objective of this study was to evaluate whether recombinant Slit2 via its receptor roundabout4 (Robo4) and the adaptor protein, Paxillin were involved in reducing BBB permeability in SBI rat model. Our results showed that endogenous Slit2 increased in the surrounding peri-resection brain tissue post-SBI, Robo4 remained unchanged and Paxillin showed a decreasing trend. Recombinant Slit2 administered 1 h before injury increased BBB junction proteins, reduced BBB permeability, and decreased neurodeficits 24 h post-SBI. Furthermore, recombinant Slit2 administration increased Rac1 activity which was reversed by Robo4 and Paxillin siRNA. Our findings suggest that recombinant Slit2 reduced SBI-induced BBB permeability, possibly by stabilizing BBB tight junction via Robo4 mediated Rac1 activation. Slit2 may be beneficial for BBB protection during elective neurosurgeries.

Phase I and Phase II Therapies for Acute Ischemic Stroke: An Update on Currently Studied Drugs in Clinical Research.

Acute ischemic stroke is a devastating cause of death and disability, consequences of which depend on the time from ischemia onset to treatment, the affected brain region, and its size. The main targets of ischemic stroke therapy aim to restore tissue perfusion in the ischemic penumbra in order to decrease the total infarct area by maintaining blood flow. Advances in research of pathological process and pathways during acute ischemia have resulted in improvement of new treatment strategies apart from restoring perfusion. Additionally, limiting the injury severity by manipulating the molecular mechanisms during ischemia has become a promising approach, especially in animal research. The purpose of this article is to review completed and ongoing phases I and II trials for the treatment of acute ischemic stroke, reviewing studies on antithrombotic, thrombolytic, neuroprotective, and antineuroinflammatory drugs that may translate into more effective treatments.

Pathophysiology and the Monitoring Methods for Cardiac Arrest Associated Brain Injury.

Cardiac arrest (CA) is a well-known cause of global brain ischemia. After CA and subsequent loss of consciousness, oxygen tension starts to decline and leads to a series of cellular changes that will lead to cellular death, if not reversed immediately, with brain edema as a result. The electroencephalographic activity starts to change as well. Although increased intracranial pressure (ICP) is not a direct result of cardiac arrest, it can still occur due to hypoxic-ischemic encephalopathy induced changes in brain tissue, and is a measure of brain edema after CA and ischemic brain injury. In this review, we will discuss the pathophysiology of brain edema after CA, some available techniques, and methods to monitor brain oxygen, electroencephalography (EEG), ICP (intracranial pressure), and microdialysis on its measurement of cerebral metabolism and its usefulness both in clinical practice and possible basic science research in development. With this review, we hope to gain knowledge of the more personalized information about patient status and specifics of their brain injury, and thus facilitating the physicians' decision making in terms of which treatments to pursue.

Pharmacological Management Options to Prevent and Reduce Ischemic Hemorrhagic Transformation.

BACKGROUND: Hemorrhagic transformation (HT) is a common and natural complication after acute ischemic stroke. The only FDA-approved treatment so far for acute ischemic stroke is rapid reperfusion with recombinant tissue plasminogen activator (rtPA). Although it has been shown to exaggerate the risk and severity of HT and to be associated with increased morbidity and mortality. OBJECTIVE: The aim of this review is to discuss the multifactorial pathophysiology of hemorrhagic transformation, promising interventional targets, and pharmacological treatment options. RESULTS AND CONCLUSION: Understanding HT is essential to restore cerebral blood flow to ischemic brain by reperfusion therapy without causing this complication and additional brain injury. Therefore methods for the prevention and treatment of HT are needed. Although experimental studies showed promising results, clinical translation remains unsatisfactory to date.

Recombinant Slit2 attenuates neuroinflammation after surgical brain injury by inhibiting peripheral immune cell infiltration via Robo1-srGAP1 pathway in a rat model.

BACKGROUND AND PURPOSE: Peripheral immune cell infiltration to the brain tissue at the perisurgical site can promote neuroinflammation after surgical brain injury (SBI). Slit2, an extracellular matrix protein, has been reported to reduce leukocyte migration. This study evaluated the effect of recombinant Slit2 and the role of its receptor roundabout1 (Robo1) and its downstream mediator Slit-Robo GTPase activating protein 1 (srGAP1)-Cdc42 on peripheral immune cell infiltration after SBI in a rat model. METHODS: One hundred and fifty-three adult male Sprague-Dawley rats (280-350 g) were used. Partial resection of right frontal lobe was performed to induce SBI. Slit2 siRNA was administered by intracerebroventricular injection 24h before SBI. Recombinant Slit2 was injected intraperitoneally 1h before SBI. Recombinant Robo1 used as a decoy receptor was co-administered with recombinant Slit2. srGAP1 siRNA was administered by intracerebroventricular injection 24h before SBI. Post-assessments included brain water content measurement, neurological tests, ELISA, Western blot, immunohistochemistry, and Cdc42 activity assay. RESULTS: Endogenous Slit2 was increased after SBI. Robo1 was expressed by peripheral immune cells. Endogenous Slit2 knockdown worsened brain edema after SBI. Recombinant Slit2 administration reduced brain edema, neurological deficits, and pro-inflammatory cytokines after SBI. Recombinant Slit2 reduced peripheral immune cell markers cluster of differentiation 45 (CD45) and myeloperoxidase (MPO), as well as Cdc42 activity in the perisurgical brain tissue which was reversed by recombinant Robo1 co-administration and srGAP1 siRNA. CONCLUSIONS: Recombinant Slit2 improved outcomes by reducing neuroinflammation after SBI, possibly by decreasing peripheral immune cell infiltration to the perisurgical site through Robo1-srGAP1 mediated inhibition of Cdc42 activity. These results suggest that Slit2 may be beneficial to reduce SBI-induced neuroinflammation.

What's New in Traumatic Brain Injury: Update on Tracking, Monitoring and Treatment.

Traumatic brain injury (TBI), defined as an alteration in brain functions caused by an external force, is responsible for high morbidity and mortality around the world. It is important to identify and treat TBI victims as early as possible. Tracking and monitoring TBI with neuroimaging technologies, including functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET), and high definition fiber tracking (HDFT) show increasing sensitivity and specificity. Classical electrophysiological monitoring, together with newly established brain-on-chip, cerebral microdialysis techniques, both benefit TBI. First generation molecular biomarkers, based on genomic and proteomic changes following TBI, have proven effective and economical. It is conceivable that TBI-specific biomarkers will be developed with the combination of systems biology and bioinformation strategies. Advances in treatment of TBI include stem cell-based and nanotechnology-based therapy, physical and pharmaceutical interventions and also new use in TBI for approved drugs which all present favorable promise in preventing and reversing TBI.

Intra-articular injection of dexketoprofen in rat knee joint: histopathologic assessment of cartilage & synovium.

BACKGROUND & OBJECTIVES: Effective pain control following outpatient surgical procedures is an important aspect of patient discharge. This study was carried out with an aim to investigate the histopathological effects of intra-articular dexketoprofen trometamol injection in knee joint on synovium and cartilage in an experimental rat model. METHODS: In each of 40 rats, the right knee was designated as the study group and the left knee as the control group (NS group). Under aseptic conditions, 35 rats received an injection of 0.25 ml (6.25 mg) dexketoprofen trometamol into the right knee joint and an injection of 0.25 ml 0.9 per cent normal saline solution into the left knee joint. On the 1st, 2nd, 7th, 14th, and 21st days after intra-articular injection, rats in specified groups were sacrificed by intraperitoneal injection of 120 mg/kg sodium thiopental. Knee joints were separated and sectioned for histopathological examination. Inflammatory changes in the joints were recorded according to a grade scale. RESULTS: No significant difference in terms of pathological changes both in synovium and cartilage was observed between the NS group and the study group on days 1, 2, 7, 14 and 21 after intra-articular injection of dexketoprofen or saline in the knee joint. INTERPRETATION & CONCLUSIONS: The findings showed no evidence of significant histopathological damage to the cartilage and synovia for a period up to 21 days following intra-articular administration of dexketoprofen trometamol in the knee joints of rats.

Preoperative ultrasound-guided suprascapular nerve block for postthoracotomy shoulder pain.

BACKGROUND: Acute postthoracotomy pain is a well-known potential problem, with pulmonary complications, ineffective respiratory rehabilitation, and delayed mobilization in the initial postoperative period, and it is followed by chronic pain. The type of thoracotomy, intercostal nerve damage, muscle retraction, costal fractures, pleural irritation, and incision scar are the most responsible mechanisms. OBJECTIVE: Our aim was to assess whether preoperative ultrasound suprascapular nerve block with thoracic epidural analgesia was effective for postthoracotomy shoulder pain relief. METHODS: Thirty-six American Society of Anesthesiologist classification physical status I-III patients (2011-2012), with a diagnosis of lung cancer and scheduled for elective open-lung surgery, were prospectively included in the study. Eighteen of the patients received an ultrasound-guided suprascapular nerve block with 10-mL 0.5% levobupivacaine, using a 22-gauge spinal needle, 1 hour before operation (group S); 18 other patients had thoracic epidural analgesia only, and no nerve block was performed. Standard general anesthesia was administered. Degree of shoulder pain was assessed by a blinded observer when discharging patients from the recovery room, and thereafter at 1, 3, 6, 12, 24, 36, 48, and 72 hours on infusion at rest and 12, 24, 36, 48, and 72 hours on coughing. The same blinded observer also recorded the total amount of epidural levobupivacaine and fentanyl used by the 2 groups. RESULTS: In the suprascapular block group, the total amount of levobupivacaine (P = 0.0001) and fentanyl (P = 0.005) used postoperatively was statistically lower than in the epidural group. Visual analogue scale measurements in the suprascapular group were statistically significantly lower at 0, 1, 3, 6, 12, 24, 36, and 48 hours than those in the epidural group, both at rest and coughing. CONCLUSION: Postthoracotomy shoulder pain reduces patient function and postsurgical rehabilitation potential after thoracotomy, and various studies on explaining the etiology and management of postthoracotomy shoulder pain have been conducted. Theories of the etiology involved either musculoskeletal origin or referred pain. In this study, we concluded that preoperative ultrasound-guided suprascapular nerve block with thoracic epidural analgesia could achieve effective shoulder pain relief for 72 hours postoperatively, both at rest and coughing.