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Hasan B Alam - One of the best experts on this subject based on the ideXlab platform.
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early resuscitation with lyophilized plasma provides equal neuroprotection compared with fresh frozen plasma in a large animal survival model of traumatic brain injury and hemorrhagic shock
Journal of Trauma-injury Infection and Critical Care, 2016Co-Authors: Ihab Halaweish, Ted Bambakidis, Ashok Srinivasan, Yongqing Li, Vahagn C Nikolian, Patrick E Georgoff, Peter James Bruhn, Patryk Piascik, Lisa Buckley, Hasan B AlamAbstract:BACKGROUND Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) is highly lethal. In previous models of combined TBI + HS, we showed that early resuscitation with fresh frozen plasma (FFP) improves neurologic outcomes. Delivering FFP, however, in austere environments is difficult. Lyophilized plasma (LP) is a logistically superior alternative to FFP, but data are limited regarding its efficacy for treatment of TBI. We conducted this study to determine the safety and long-term outcomes of early treatment with LP in a large animal model of TBI + HS. METHODS Adult anesthetized swine underwent TBI and volume-controlled hemorrhage (40% blood volume) concurrently. After 2 hours of shock, Animals were randomized (n = 5 per /group) to FFP or LP (1× shed blood) treatment. Serial blood gases were drawn, and thromboelastography was performed on citrated, kaolin-activated whole-blood samples. Five hours after treatment, packed red blood cells were administered, and Animals recovered. A 32-point Neurologic Severity Score was assessed daily for 30 days (0 = normal, 32 = most severe injury). Cognitive functions were tested by Training Animals to retrieve food from color-coded boxes. Brain lesion size was measured on serial magnetic resonance imaging, and an autopsy was performed at 30 days. RESULTS The severity of shock and the degree of resuscitation were similar in both groups. Administration of FFP and LP was well tolerated with no differences in reversal of shock or thromboelastography parameters. Animals in both groups displayed the worst Neurologic Severity Score on postoperative Day 1 with rapid recovery and return to baseline within 7 days of injury. Lesion size on Day 3 in FFP-treated Animals was 645 ± 85 versus 219 ± 20 mm 3 in LP-treated Animals (p < 0.05). There were no differences in cognitive functions or delayed treatment-related complications. CONCLUSIONS Early treatment with LP in TBI + HS is safe and provides neuroprotection that is comparable to FFP.
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early resuscitation with fresh frozen plasma for traumatic brain injury combined with hemorrhagic shock improves neurologic recovery
Journal of The American College of Surgeons, 2015Co-Authors: Ihab Halaweish, Ted Bambakidis, Wei He, Durk Linzel, Zhigang Chang, Ashok Srinivasan, Simone E Dekker, Yongqing Li, Hasan B AlamAbstract:Background We have shown that early administration of fresh frozen plasma (FFP) reduces the size of brain lesions 6 hours after injury in a large animal model of traumatic brain injury (TBI) and hemorrhagic shock (HS). To examine long-term outcomes, we hypothesized that early treatment with FFP would result in faster neurologic recovery and better long-term outcomes in a combined TBI and HS model. Study Design Anesthetized Yorkshire swine underwent combined TBI and volume-controlled hemorrhage (40% blood volume). After 2 hours of shock, Animals were randomized (n = 5/group) to normal saline (3× shed blood) or FFP (1× shed blood) treatment. A neurologic severity score was assessed for 30 days. Magnetic resonance imaging of the brain was performed at days 3, 10, and 24. Cognitive function was tested by Training Animals to retrieve food from color-coded boxes. Results Neurologic impairment was lower and speed of recovery was considerably faster in the FFP-treated Animals. There was a trend toward a smaller lesion size in FFP-treated animal at days 3 and 10, but this did not reach statistical significance. Both groups reached baseline performance on the cognitive testing; however, FFP-treated Animals were able to participate, on average, 8 days earlier due to quicker recovery. Conclusions This is the first study to demonstrate the beneficial effects of FFP treatment in a long-term survival model of combined TBI and HS. Our data show that early treatment with FFP substantially attenuates the degree of neurologic impairment, improves the rate of recovery, and preserves the cognitive functions.
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learning and memory is preserved after induced asanguineous hyperkalemic hypothermic arrest in a swine model of traumatic exsanguination
Surgery, 2002Co-Authors: Hasan B Alam, Mark W Bowyer, Elena Koustova, Vadim GushchinAbstract:Background. Induced asanguineous hypothermic metabolic arrest (suspended animation) could provide valuable time to repair major vascular injuries if safely induced in patients with trauma. We report a novel method of doing this in a swine model of uncontrolled lethal hemorrhage (ULH) that resulted in preservation of learning ability and memory. Methods. Yorkshire swine (100 to 125 lb) underwent ULH before rapid intra-aortic infusion of a hypothermic (4°C), hyperkalemic (70 mEq/L) organ preservation solution by a left thoracotomy. Cooling continued until core temperature reached 10°C, and this was maintained for 60 minutes using low-flow cardiopulmonary bypass. Vascular injuries were repaired during this state of suspended animation, which was then reversed, and the Animals were observed for 6 weeks. Cognitive functions were tested by Training Animals to retrieve food from color-coded boxes. Postoperatively, the ability to remember this task and a 75-point objective neurologic scale were used to test neurologic function. In experiment I, ULH was caused by lacerating thoracic aorta (n = 9). Five preoperatively untrained Animals were trained to perform the task and compared with control Animals (n = 15), and 4 preoperatively trained Animals were tested for memory retention postoperatively. In experiment II, ULH was induced by creating an iliac artery and vein injury (n = 15). Animals were kept in shock for 15, 30, and 60 minutes before the induction of hypothermia. Results. In experiment I, surviving Animals (7/9) were neurologically intact, and their capacity to learn new skills was no different than for control Animals. All pretrained Animals demonstrated complete memory retention. In experiment II, survival with 15, 30, and 60 minutes of shock were 80%, 60%, and 80%, respectively. All Animals (except 1) in the 60-minute group were neurologically intact and displayed normal learning capacity. Conclusions. Induction of hypothermic metabolic arrest (by thoracotomy) for repair of complex traumatic injuries is feasible with preservation of normal neurologic function, even after extended periods of shock from an intra-abdominal source of uncontrolled hemorrhage. (Surgery 2002;132:278-88.)
Amir Dezfouli - One of the best experts on this subject based on the ideXlab platform.
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learning the structure of the world the adaptive nature of state space and action representations in multi stage decision making
PLOS Computational Biology, 2019Co-Authors: Amir Dezfouli, Bernard W BalleineAbstract:State-space and action representations form the building blocks of decision-making processes in the brain; states map external cues to the current situation of the agent whereas actions provide the set of motor commands from which the agent can choose to achieve specific goals. Although these factors differ across environments, it is currently unknown whether or how accurately state and action representations are acquired by the agent because previous experiments have typically provided this information a priori through instruction or pre-Training. Here we studied how state and action representations adapt to reflect the structure of the world when such a priori knowledge is not available. We used a sequential decision-making task in rats in which they were required to pass through multiple states before reaching the goal, and for which the number of states and how they map onto external cues were unknown a priori. We found that, early in Training, Animals selected actions as if the task was not sequential and outcomes were the immediate consequence of the most proximal action. During the course of Training, however, rats recovered the true structure of the environment and made decisions based on the expanded state-space, reflecting the multiple stages of the task. Similarly, we found that the set of actions expanded with Training, although the emergence of new action sequences was sensitive to the experimental parameters and specifics of the Training procedure. We conclude that the profile of choices shows a gradual shift from simple representations to more complex structures compatible with the structure of the world.
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learning the structure of the world the adaptive nature of state space and action representations in multi stage decision making
bioRxiv, 2017Co-Authors: Amir Dezfouli, Bernard W BalleineAbstract:State-space and action representations form the building blocks of decision-making processes in the brain; states map external cues to the current situation of the agent whereas actions provide the set of motor commands from which the agent can choose to achieve specific goals. Although these factors differ across environments, it is not currently known whether or how accurately state and action representations are acquired by the agent because previous experiments have typically provided this information a priori through instruction or pre-Training. Here we show that, in the absence of such a priori knowledge, state and action representations adapt to reflect the structure of the world. We used a sequential decision-making task in rats in which they were required to pass through multiple states before reaching the goal, and for which the number of states and how they map onto external cues were not known a priori. We found that, early in Training, Animals selected actions as if the task was not sequential and outcomes were the immediate consequence of the most proximal action. During the course of Training, however, rats recovered the true structure of the environment and made decisions based on the expanded state-space, reflecting the multiple stages of the task. We found a similar pattern with actions; early in Training Animals only considered the execution of single actions whereas, after Training, they created useful action sequences that expanded the set of available actions. We conclude that the profile of choices shows a gradual shift from simple representations of actions and states to more complex structures compatible with the structure of the world.
Nathalie Breysse - One of the best experts on this subject based on the ideXlab platform.
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rodent model of attention the 5 choice serial reaction time task
Current protocols in pharmacology, 2008Co-Authors: Guy A Higgins, Nathalie BreysseAbstract:The 5-choice serial reaction time task (5-CSRTT) is the most widely used test to measure attentional performance in rodents. The basic test design involves Training Animals to respond to a brief visual stimulus presented unpredictably in one of five locations. Once trained to stable performance levels, the effects of experimental manipulations on response speed and choice accuracy are measured and each are related to attentional performance. Increasingly, the test is also used to examine aspects of response control. Having been adapted from a human task, the test has also been successfully extended to the mouse and primate, thus highlighting its translational value. Increasingly this test is being applied in drug discovery efforts, primarily to identify novel drug treatments for conditions associated with attention deficits. Curr. Protoc. Pharmacol. 41:5.49.1-5.49.20. © 2008 by John Wiley & Sons, Inc. Keywords: attention; cognition; methodology; rat; mouse; drug discovery; nicotine
Bernard W Balleine - One of the best experts on this subject based on the ideXlab platform.
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learning the structure of the world the adaptive nature of state space and action representations in multi stage decision making
PLOS Computational Biology, 2019Co-Authors: Amir Dezfouli, Bernard W BalleineAbstract:State-space and action representations form the building blocks of decision-making processes in the brain; states map external cues to the current situation of the agent whereas actions provide the set of motor commands from which the agent can choose to achieve specific goals. Although these factors differ across environments, it is currently unknown whether or how accurately state and action representations are acquired by the agent because previous experiments have typically provided this information a priori through instruction or pre-Training. Here we studied how state and action representations adapt to reflect the structure of the world when such a priori knowledge is not available. We used a sequential decision-making task in rats in which they were required to pass through multiple states before reaching the goal, and for which the number of states and how they map onto external cues were unknown a priori. We found that, early in Training, Animals selected actions as if the task was not sequential and outcomes were the immediate consequence of the most proximal action. During the course of Training, however, rats recovered the true structure of the environment and made decisions based on the expanded state-space, reflecting the multiple stages of the task. Similarly, we found that the set of actions expanded with Training, although the emergence of new action sequences was sensitive to the experimental parameters and specifics of the Training procedure. We conclude that the profile of choices shows a gradual shift from simple representations to more complex structures compatible with the structure of the world.
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learning the structure of the world the adaptive nature of state space and action representations in multi stage decision making
bioRxiv, 2017Co-Authors: Amir Dezfouli, Bernard W BalleineAbstract:State-space and action representations form the building blocks of decision-making processes in the brain; states map external cues to the current situation of the agent whereas actions provide the set of motor commands from which the agent can choose to achieve specific goals. Although these factors differ across environments, it is not currently known whether or how accurately state and action representations are acquired by the agent because previous experiments have typically provided this information a priori through instruction or pre-Training. Here we show that, in the absence of such a priori knowledge, state and action representations adapt to reflect the structure of the world. We used a sequential decision-making task in rats in which they were required to pass through multiple states before reaching the goal, and for which the number of states and how they map onto external cues were not known a priori. We found that, early in Training, Animals selected actions as if the task was not sequential and outcomes were the immediate consequence of the most proximal action. During the course of Training, however, rats recovered the true structure of the environment and made decisions based on the expanded state-space, reflecting the multiple stages of the task. We found a similar pattern with actions; early in Training Animals only considered the execution of single actions whereas, after Training, they created useful action sequences that expanded the set of available actions. We conclude that the profile of choices shows a gradual shift from simple representations of actions and states to more complex structures compatible with the structure of the world.
Balazs Hangya - One of the best experts on this subject based on the ideXlab platform.
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efficient Training of mice on the 5 choice serial reaction time task in an automated rodent Training system
Scientific Reports, 2020Co-Authors: Eszter Birtalan, Anita Banhidi, Joshua I Sanders, Diana Balazsfi, Balazs HangyaAbstract:Experiments aiming to understand sensory-motor systems, cognition and behavior necessitate Training Animals to perform complex tasks. Traditional Training protocols require lab personnel to move the Animals between home cages and Training chambers, to start and end Training sessions, and in some cases, to hand-control each Training trial. Human labor not only limits the amount of Training per day, but also introduces several sources of variability and may increase animal stress. Here we present an automated Training system for the 5-choice serial reaction time task (5CSRTT), a classic rodent task often used to test sensory detection, sustained attention and impulsivity. We found that full automation without human intervention allowed rapid, cost-efficient Training, and decreased stress as measured by corticosterone levels. Training breaks introduced only a transient drop in performance, and mice readily generalized across Training systems when transferred from automated to manual protocols. We further validated our automated Training system with wireless optogenetics and pharmacology experiments, expanding the breadth of experimental needs our system may fulfill. Our automated 5CSRTT system can serve as a prototype for fully automated behavioral Training, with methods and principles transferrable to a range of rodent tasks.