scholarly journals Treatment of Swine Closed Head Injury with Perfluorocarbon NVX-428

2020 ◽  
Vol 8 (4) ◽  
pp. 41
Author(s):  
Francoise Arnaud ◽  
Ashraful Haque ◽  
MAJ Erin Morris ◽  
Paula Moon-Massat ◽  
Charles Auker ◽  
...  

Pre-hospital treatment of traumatic brain injury (TBI) with co-existing polytrauma is complicated by requirements for intravenous fluid volume vs. hypotensive resuscitation. A low volume, small particle-size-oxygen-carrier perfluorocarbon emulsion NVX-428 (dodecafluoropentane emulsion; 2% w/v) could improve brain tissue with minimal additional fluid volume. This study examined whether the oxygen-carrier NVX-428 shows safety and efficacy for pre-hospital treatment of TBI. Anesthetized swine underwent fluid percussion injury TBI and received 1 mL/kg IV NVX-428 (TBI-NVX) at 15 min (T15) or normal saline (no-treatment) (TBI-NON). Similarly, uninjured swine received NVX-428 (SHAM-NVX) or normal saline (SHAM-NON). Animals were monitored and measurements were taken for physiological and neurological parameters before euthanasia at the six-hour mark (T360). Histopathological analysis was performed on paraffin embedded tissues. Physiological, biochemical and blood gas parameters were not different, with the exception of a significant but transient increase in mean pulmonary artery pressure observed in the TBI-experimental group immediately after drug administration. There were no initial differences in brain oxygenation at baseline, but over time oxygen decreased ~50% in both TBI groups. Histological brain injury scores were similar between TBI-NVX and TBI-NON, although a number of subcategories (spongiosis-ischemic/dead neurons-hemorrhage-edema) in TBI-NVX had a tendency for lower scores. The cerebellum showed significantly lower spongiosis and ischemic/dead neuron injury scores and a lower number of Fluoro-Jade-B-positive cerebellar-Purkinje-cells after NVX-428 treatment compared to controls. NVX-428 may assist in mitigating secondary cellular brain damage.

2014 ◽  
pp. 83-89
Author(s):  
Dung Ngo ◽  
Thi Nhan Nguyen ◽  
Khanh Hoang

Objective: Study on 106 patients with closed head injury, assessment of serum ADH concentration, correlation with Glasgow score, sodium and plasma osmotic pressure. Patients and methods: Patients with closed head injuries were diagnosed determined by computerized tomography, admitted to the Hue Central Hospital 72 hours ago. Results: (i) Serum concentration of ADH 42.21 ± 47.80 pg/ml. (ii) There is a negative correlation between serum levels of ADH with: (1) Glasgow point r = -0.323, p <0.01; (2) Plasma sodium concentration r = - 0.211, p > 0.05; (3) Plasma osmotic pressure r = - 0.218, p> 0.05. Conclusion: There is a negative correlation between serum levels of ADH with Glasgow scale, plasma sodium concentration and osmotic pressure in plasma. Key words: ADH traumatic brain injury.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 500
Author(s):  
William Brad Hubbard ◽  
Meenakshi Banerjee ◽  
Hemendra Vekaria ◽  
Kanakanagavalli Shravani Prakhya ◽  
Smita Joshi ◽  
...  

Traumatic brain injury (TBI) affects over 3 million individuals every year in the U.S. There is growing appreciation that TBI can produce systemic modifications, which are in part propagated through blood–brain barrier (BBB) dysfunction and blood–brain cell interactions. As such, platelets and leukocytes contribute to mechanisms of thromboinflammation after TBI. While these mechanisms have been investigated in experimental models of contusion brain injury, less is known regarding acute alterations following mild closed head injury. To investigate the role of platelet dynamics and bioenergetics after TBI, we employed two distinct, well-established models of TBI in mice: the controlled cortical impact (CCI) model of contusion brain injury and the closed head injury (CHI) model of mild diffuse brain injury. Hematology parameters, platelet-neutrophil aggregation, and platelet respirometry were assessed acutely after injury. CCI resulted in an early drop in blood leukocyte counts, while CHI increased blood leukocyte counts early after injury. Platelet-neutrophil aggregation was altered acutely after CCI compared to sham. Furthermore, platelet bioenergetic coupling efficiency was transiently reduced at 6 h and increased at 24 h post-CCI. After CHI, oxidative phosphorylation in intact platelets was reduced at 6 h and increased at 24 h compared to sham. Taken together, these data demonstrate that brain trauma initiates alterations in platelet-leukocyte dynamics and platelet metabolism, which may be time- and injury-dependent, providing evidence that platelets carry a peripheral signature of brain injury. The unique trend of platelet bioenergetics after two distinct types of TBI suggests the potential for utilization in prognosis.


2008 ◽  
Vol 23 (4) ◽  
pp. 320-326 ◽  
Author(s):  
Michael J. Makley ◽  
Lisa Johnson-Greene ◽  
Patrick M. Tarwater ◽  
Andrew J. Kreuz ◽  
J. Spiro ◽  
...  

Objective. Sleep disturbance is common in the subacute recovery phase following brain injury. A previous study from the authors' group found 68% of patients with closed head injury (CHI) had disrupted sleep on a rehabilitation unit. In the present study, the authors investigated whether improvement in sleep efficiency correlates with duration of posttraumatic amnesia (PTA) after CHI. Methods. Fourteen CHI patients were enrolled and followed prospectively. Mechanism of injury included motor vehicle accident, fall, and blunt assault. An actigraph was placed on each subject's wrist within 72 hours of admission to the rehabilitation unit and recorded data for the duration of their stay. A minimum of 7 days of continuous actigraphy data was obtained on all subjects. PTA was measured daily using the Orientation Log (O-LOG). Results. Seventy-eight percent of subjects had mean week-1 sleep efficiency scores of ≤63%. Patients admitted having already cleared PTA had significantly better week-1 sleep efficiency scores than those with ongoing amnesia ( P = .032). For those patients admitted with ongoing PTA, each 10-unit increase in sleep efficiency score correlated with 1 unit increase in O-LOG score ( P = .056). Conclusions. Disrupted sleep is common in the postacute stage following CHI. Improved sleep efficiency correlates with resolution of PTA. Decreased sleep efficiency may negatively affect memory return after traumatic brain injury. Actigraphy is uniquely suited to study the sleep patterns of these patients.


2012 ◽  
Vol 27 (4) ◽  
pp. 290-294 ◽  
Author(s):  
Danilo dos Santos Silva ◽  
José Nazareno Pearce de Oliveira Brito ◽  
Jerúsia Oliveira Ibiapina ◽  
Marcel Fernando Miranda Batista Lima ◽  
Andréa Ribeiro Gonçalves de Vasconcelos Medeiros ◽  
...  

PURPOSE: To study histopathological findings due to a model of closed head injury by weight loss in rats. METHODS: A platform was used to induce closed cranial lesion controlled by weight loss with a known and predefined energy. 25 male Wistar rats (Rattus novergicus albinus) were divided in five equal groups which received different cranial impact energy levels: G1, G2, G3 and G4 with 0.234J, 0.5J, 0.762J and 1J respectively and G5 (Sham). Under the effect of analgesia, the brain of each group was collected and prepared for histopathological analysis by conventional optic microscopy. RESULTS: It was observed greater number of injured neurons in animals of group 4, however neuronal death also could be noticed in animals of group 5. Intraparenchymal hemorrhages were more frequent in animals of group 4 and the cytotoxic brain swelling and vascular congestion were more intense in this group CONCLUSION: The histopathological analysis of these findings allowed to observe typical cranial trauma alterations and these keep close relation with impact energy.


2008 ◽  
Vol 108 (3) ◽  
pp. 575-587 ◽  
Author(s):  
Guy Rosenthal ◽  
Diane Morabito ◽  
Mitchell Cohen ◽  
Annina Roeytenberg ◽  
Nikita Derugin ◽  
...  

Object Traumatic brain injury (TBI) often occurs as part of a multisystem trauma that may lead to hemorrhagic shock. Effective resuscitation and restoration of oxygen delivery to the brain is important in patients with TBI because hypotension and hypoxia are associated with poor outcome in head injury. We studied the effects of hemoglobin-based oxygen-carrying (HBOC)–201 solution compared with lactated Ringer (LR) solution in a large animal model of brain injury and hemorrhage, in a blinded prospective randomized study. Methods Swine underwent brain impact injury and hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Twenty swine were randomized to undergo resuscitation with HBOC-201 (6 ml/kg) or LR solution (12 ml/kg) and were observed for an average of 6.5 ± 0.5 hours following resuscitation. At the end of the observation period, magnetic resonance (MR) imaging was performed. Histological studies of swine brains were performed using Fluoro-Jade B, a marker of early neuronal degeneration. Results Swine resuscitated with HBOC-201 had higher MAP, higher cerebral perfusion pressure (CPP), improved base deficit, and higher brain tissue oxygen tension (PbtO2) than animals resuscitated with LR solution. No significant difference in total injury volume on T2-weighted MR imaging was observed between animals resuscitated with HBOC-201 solution (1155 ± 374 mm3) or LR solution (1246 ± 279 mm3; p = 0.55). On the side of impact injury, no significant difference in the mean number of Fluoro-Jade B–positive cells/hpf was seen between HBOC-201 solution (61.5 ± 14.7) and LR solution (48.9 ± 17.7; p = 0.13). Surprisingly, on the side opposite impact injury, a significant increase in Fluoro-Jade B–positive cells/hpf was seen in animals resuscitated with LR solution (42.8 ± 28.3) compared with those resuscitated with HBOC-201 solution (5.6 ± 8.1; p < 0.05), implying greater neuronal injury in LR-treated swine. Conclusions The improved MAP, CPP, and PbtO2 observed with HBOC-201 solution in comparison with LR solution indicates that HBOC-201 solution may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. The use of HBOC-201 solution appears to decrease cellular degeneration in the brain area not directly impacted by the primary injury. Hemoglobin-based oxygen-carrying–201 solution may act by improving cerebral blood flow or increasing the oxygen-carrying capacity of blood, mitigating a second insult to the injured brain.


1991 ◽  
Vol 3 (1) ◽  
pp. 25-41 ◽  
Author(s):  
Nancy L. Etcoff ◽  
Roy Freeman ◽  
Kyle R. Cave

Prosopagnosia is a neurological syndrome in which patients cannot recognize faces. Kecently it has been shown that some prosopagnosics give evidence of "covert" recognition: they show greater autonomic responses to familiar faces than to unfamiliar ones, and respond differently to familiar faces in learning and interference tasks. Although some patients do not show covert recognition, this has usually been attributed to an "apperceptive" deficit that impairs perceptual analysis of the input. The implication is that prosopagnosia is a deficit in access to, or awareness of, memories of faces: the inducing brain injury does not destroy the memories themselves. We present a case study that challenges this view. LH suffers from prosopagnosia as the result of a closed head injury. He cannot recognize familiar faces or report that they are familiar, nor answer questions about the faces from memory, though he can (1) recognize common objects and subtly varying shapes, (2) match faces while ignoring irrelevant information such as emotional expression or angle of view, (3) recognize sex, age, and like-ability from faces, and (4) recognize people by a number of nonfacial channels. The only other categories of shapes that he has marked trouble recognizing are animals and emotional expressions, though even these impairments were not as severe as the one for faces. Three measures (sympathetic skin response, pupil dilation, and learning correct and incorrect names of faces) failed to show any signs of covert face recognition in LH, though the measures were sensitive enough to reflect autonomic reactions in LH to stimuli other than faces, and face familiarity in normal controls. Thus prosopagnosia cannot always be attributed to a mere absence of awareness (i.e., preserved information about faces whose output is disconnected from conscious cognitive processing), to an apperceptive deficit (i.e., preserved information about faces that cannot be accessed due to improperly analyzed perceptual input), or to an inability to recognize complex or subtly varying shapes (i.e., loss or degradation of shape memory in general). We conclude that it is possible for brain injury to eliminate the storage of information about familiar faces and certain related shapes.


2004 ◽  
Vol 126 (4) ◽  
pp. 523-528 ◽  
Author(s):  
P. V. Bayly, ◽  
S. Ji, ◽  
S. K. Song, ◽  
R. J. Okamoto, ◽  
P. Massouros, ◽  
...  

Two-dimensional (2-D) strain fields were estimated non-invasively in two simple experimental models of closed-head brain injury. In the first experimental model, shear deformation of a gel was induced by angular acceleration of its spherical container. In the second model the brain of a euthanized rat pup was deformed by indentation of its skull. Tagged magnetic resonance images (MRI) were obtained by gated image acquisition during repeated motion. Harmonic phase (HARP) images corresponding to the spectral peaks of the original tagged MRI were obtained, following procedures proposed by Osman, McVeigh and Prince [1]. Two methods of HARP strain analysis were applied, one based on the displacement of tag line intersections, and the other based on the gradient of harmonic phase. Strain analysis procedures were also validated on simulated images of deformed grids. Results show that it is possible to visualize deformation and to quantify strain efficiently in animal models of closed head injury.


2020 ◽  
Vol 21 (21) ◽  
pp. 8256 ◽  
Author(s):  
Min Kyu Park ◽  
Bo Young Choi ◽  
A Ra Kho ◽  
Song Hee Lee ◽  
Dae Ki Hong ◽  
...  

Traumatic brain injury (TBI) can cause physical, cognitive, social, and behavioral changes that can lead to permanent disability or death. After primary brain injury, translocated free zinc can accumulate in neurons and lead to secondary events such as oxidative stress, inflammation, edema, swelling, and cognitive impairment. Under pathological conditions, such as ischemia and TBI, excessive zinc release, and accumulation occurs in neurons. Based on previous research, it hypothesized that calcium as well as zinc would be influx into the TRPC5 channel. Therefore, we hypothesized that the suppression of TRPC5 would prevent neuronal cell death by reducing the influx of zinc and calcium. To test our hypothesis, we used a TBI animal model. After the TBI, we immediately injected NU6027 (1 mg/kg, intraperitoneal), TRPC5 inhibitor, and then sacrificed animals 24 h later. We conducted Fluoro-Jade B (FJB) staining to confirm the presence of degenerating neurons in the hippocampal cornus ammonis 3 (CA3). After the TBI, the degenerating neuronal cell count was decreased in the NU6027-treated group compared with the vehicle-treated group. Our findings suggest that the suppression of TRPC5 can open a new therapeutic window for a reduction of the neuronal death that may occur after TBI.


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