Ablation Injury Research Articles

Acute injury immediately post atrial fibrillation ablation defined by MRI

Catheter ablation is effective in symptomatic, drug refractory atrial fibrillation and can result in cure but success rates vary significantly with recurrences ranging from 40-86%. In the months following ablation, LA wall scarring on late gadolinium enhancement (LGE) is useful for determining the location and extent of injury and has been used to guide follow up ablation to 'close the gaps' after unsuccessful PVAI. More recently, imaging acute ablation injury using double inversion recovery (DIR) sequences has been shown feasible and has generated interest for its potential clinical value in guiding ablations.

Percutaneous Microwave Ablation or Nephrectomy for VX-2 Carcinoma in Rabbit Kidney

We compared the effectiveness of percutaneous microwave ablation and radical nephrectomy for implanted VX-2 carcinoma in rabbit kidneys. VX-2 tumors were surgically implanted into the left lower pole parenchyma of 26 New Zealand White rabbit kidneys. At 12 days after implantation implanted rabbits were randomly assigned to 1 of 3 groups according to therapy type, including percutaneous microwave ablation, nephrectomy and no treatment. The anticancer effect and safety were compared among the groups. Histopathological changes in tumor tissue with time after microwave ablation were evaluated. The survival rate in the percutaneous microwave ablation group was significantly higher than that in the no treatment group and showed no statistically significant difference compared with that in the nephrectomy group. Serum creatinine did not increase after microwave therapy but we noted a statistically significant serum creatinine increase in the nephrectomy group. Histological analysis revealed completely coagulative necrosis of the tumor in 10 of 12 rabbits (83.3%) after microwave ablation. Two rabbits died, including 1 of peritonitis in the nephrectomy group and 1 of intestinal fistula due to heat injury in the percutaneous microwave ablation group. This study shows that percutaneous microwave ablation can achieve effects similar to those of radical nephrectomy. It caused no significant changes in renal function when treating implanted VX-2 renal tumors. Percutaneous microwave ablation has the potential of being a minimally invasive treatment for small renal tumors.

Complete ablation of a renal tumor abutting the inferior vena cava using a radiofrequency electrode as a lever: A case report

Radiofrequency ablation is accepted as a minimally invasive treatment for renal tumors in patients who are poor candidates for surgery. However, ablation of tumors that abut large vessels is likely to be incomplete due to the heat-sink effect or may result in vascular injury. We report a case of a renal tumor abutting the inferior vena cava, which was successfully treated with radiofrequency ablation, with an emphasis on the technical aspects required to avoid both incomplete ablation and vascular injury by using a radiofrequency electrode as a lever.

Why can pulmonary vein stenoses created by radiofrequency catheter ablation worsen during and after follow-up ? A potential explanation

BackgroundRadiofrequency catheter ablation of excitation foci inside pulmonary veins (PV) generates stenoses that can become quite severe during or after the follow-up period. Since severe PV stenoses have most often disastrous consequences, it would be important to know the underlying mechanism of this temporal evolution. The present study proposes a potential explanation based on mechanical considerations.Methodswe have used a mathematical-physical model to examine the cyclic increase in axial wall stress induced in the proximal (= upstream), non-stenosed segment of a stenosed pulmonary vein during the forward flow phases. In a representative example, the value of this increase at peak flow was calculated for diameter stenoses (DS) ranging from 1 to 99%.ResultsThe increase becomes appreciable at a DS of roughly 30% and rise then strongly with further increasing DS value. At high DS values (e.g. > 90%) the increase is approximately twice the value of the axial stress present in the PV during the zero-flow phase.ConclusionSince abnormal wall stresses are known to induce damages and abnormal biological processes (e.g., endothelium tears, elastic membrane fragmentations, matrix secretion, myofibroblast generation, etc) in the vessel wall, it seems plausible that the supplementary axial stress experienced cyclically by the stenotic and the proximal segments of the PV is responsible for the often observed progressive reduction of the vessel lumen after healing of the ablation injury. In the light of this model, the only potentially effective therapy in these cases would be to reduce the DS as strongly as possible. This implies most probably stenting or surgery.

Difference in Humoral Biomarkers for Myocardial Injury and Inflammation in Radiofrequency Ablation versus Cryoablation

Markers of myocardial injury and inflammation have been shown to be elevated following radiofrequency (RF) ablation. This study aimed to compare RF ablation and cryoablation for their impact on markers for myocardial injury and inflammation. Nineteen patients received catheter ablation for atrial flutter by either cryoablation (10 patients) or open-irrigated RF ablation (nine patients). Venous blood samples for troponin T (TnT), creatinkinase (CK), and the cardiac isoenzyme MB (CKMB) were obtained before, at six hours after the end of ablation, and the following day. C-reactive protein (CRP) levels were measured before ablation and the following day. Bidirectional isthmus block was achieved in all patients. Cryoablation showed significantly higher TnT following ablation (0.85 microg/l +/- 0.39 microg/l) compared to RF ablation (0.36 microg/l +/- 0.24 microg/l; p= 0.01) with declining levels the following day (cryoablation: 0.58 microg/l +/- 0.20 microg/l; RF ablation 0.34 microg/l +/- 0.21 microg/l; p= 0.03). We observed equal findings for CK and CKMB, both significantly higher in cryoablation. RF ablation led to a nonsignificant rise in CK and CKMB. CRP was elevated significantly higher following RF ablation (12.3 mg/dl +/- 4.1 mg/dl) compared to cryoablation (6.9 mg/dl +/- 4.0 mg/dl; p= 0.01). We show reduced inflammation despite higher markers for myocardial injury in cryoablation. The difference in biomarkers reflects different lesion formation in cryoablation and RF ablation. Cryoablation shows less systemic inflammatory reaction. This might be due to less endothelial damage and surface thrombosis in cryoablation.

Esophageal Injury in Patients Status Post Cardiac Catheter Radiofrequency Ablation for Atrial Fibrillation: A Potential Precursor to Fatal Atrial-Esophageal Fistula?

Background: Catheter ablation is becoming a standard therapy for atrial fibrillation (AF) in patients in whom at least one class I or class III anti-arrhythmic drug has failed to control the AF. Since 2004 there have been reports of left atrial-esophageal fistulae following percutaneous catheter ablation using pulmonary vein isolation for atrial fibrillation. Left atrial-esophageal fistulae usually become clinically apparent 3-21 days post-ablation and twelve of the fourteen cases reported in the literature resulted in death. Aim: To prospectively assess esophageal mucosal injury and symptoms in patients after catheter ablation for AF. Patients & Methods: Between July 25th, 2006 and September 30th, 2006, all patients at our university center referred for cardiac catheter radiofrequency ablation were offered an EGD one day following the procedure, immediately preceding a regularly scheduled trans-esophageal echocardiogram. Any mucosal abnormality was photo-documented and measured with a reference forceps. Patients with mucosal injury were treated with high dose PPI and sucralfate slurry. Two week follow-up endoscopy was performed in patients with mucosal injury. Results: Twelve consecutive patients were evaluated. Five of the twelve patients had mid esophageal ulcers identified endoscopically the day following catheter ablation for atrial fibrillation. Only three of the five ulcer patients reported any subjective symptoms: two had mild chest pain and one had odynophagia. These ulcers ranged in size from 5 to 12 mm in length. Three patients had repeat EGDs two weeks after ablation: one had a residual healing ulcer while the other two had healed ulcers with normal appearing mucosa. No adverse outcomes were reported in any of the patients. Conclusions: Our prospective series is the first to date to investigate the incidence of esophageal injury in radio-frequency ablation for atrial fibrillation. Results of this study show that esophageal injury accompanying cardiac catheter ablation is common. These ulcers are likely a manifestation of transmural injury that provides the substrate for the catastrophic complication of atrial-esophageal fistula formation. Measures are needed to prevent this injury and endoscopic monitoring can serve as a means to asses the efficacy of preventive measures. Endoscopists must be aware of this cause of mucosal abnormalities post-cardiac radiofrequency ablation.

Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury

Neurotrophins have been shown to promote axonal growth and regeneration after spinal cord injury. The therapeutic utility of neurotrophins may be enhanced by using a controlled delivery system to increase the duration of neurotrophin availability following injury. Such a delivery system can be incorporated into a bioactive scaffold to serve as a physical bridge for regeneration. This study assessed the effect of controlled delivery of neurotrophin-3 (NT-3) from fibrin scaffolds implanted in spinal cord lesions immediately following 2-mm ablation injury in adult rats. Nine days after injury, fibrin scaffolds containing the delivery system and NT-3 (1000 ng/mL) elicited more robust neuronal fiber growth into the lesion than did control scaffolds or saline (1.5- to 3-fold increase). Implantation of fibrin scaffolds resulted in a dramatic reduction of glial scar formation at the white matter border of the lesion. Hindlimb motor function of treated animals did not improve relative to controls at 12 weeks post-injury. Thus, controlled delivery of NT-3 from fibrin scaffolds enhanced the initial regenerative response by increasing neuronal fiber sprouting and cell migration into the lesion, while functional motor recovery was not observed in this model.

Following Protocols Reduces Endometrial Ablation Injury

Following Protocols Reduces Endometrial Ablation Injury

Immunohistochemical Localization of EGF, TGF-α, TGF-β, and Their Receptors in Rat Corneas During Healing of Excimer Laser Ablation

Purpose: Members of the epidermal growth factor (EGF) and transforming growth factor beta (TGF-β) families of growth factors and receptors are known to regulate key aspects of corneal wound healing, including epithelial migration and scar formation. To further understand their roles, mRNA levels were measured and proteins were immunolocalized in rat corneas at multiple time points during healing of excimer laser ablation injury. Methods: Excimer laser photoablation was performed to a depth of 50 μm on rat corneas. Levels of mRNAs for EGF, TGF-α, TGF-β isoforms 1, 2, and 3, and their receptors (EGF-R and TGFβ-IIR) were measured by quantitative RT-PCR on days 0, 1.5, 7, 21, 42, and 91 after ablation. Immunohistochemical localization of the growth factors and their receptors was performed on days 0, 7, and 21 in corneal sections. Results: Levels of EGF mRNA remained stable in rat corneas after ablation (68 ± 12 copies/cell, mean ± SD), whereas levels of TGF-α mRNA progressively increased sixfold to a maximum at day 42 (300 copies/cell) then slightly decreased on day 91. Levels of EGF-R mRNA rapidly increased 60-fold on day 7 compared with day 0 (571 vs. 9 copies/cell) then decreased sixfold above baseline at day 91. Levels of TGF-β1 mRNA remained stable (36 ± 10 copies/cell), whereas levels of TGF-β2 and TGF-β3 mRNAs peaked on day 21 (300-fold and 25-fold increase) and remained elevated through day 91. Levels of TGFβ-IIR mRNA showed a similar pattern. Immunostaining of all the growth factors and receptors was primarily in basal layers of epithelial cells in uninjured cornea and during healing. Intensity of immunostaining for TGF-β1, TGFβ-IR, and TGFβ-IIR increased appreciably in the basal epithelial layers after ablation. Conclusions: Levels of mRNAs for several key members of the EGF and TGF-β systems increase during corneal wound healing. In addition, the proteins are primarily localized in basal layers of epithelial cells, which suggest these cells are active in synthesizing autocrine and paracrine growth factors that modulate corneal wound healing.

Patterns of heat shock protein (HSP70) expression and Kupffer cell activity following thermal ablation of liver and colorectal liver metastases

The time course and extent of thermal ablative injury differs in liver compared to tumour tissue. This may be influenced by differences in the expression of heat shock proteins (HSP) and the response of Kupffer cells to thermal injury. This study determines the expression and response of HSP70 and Kupffer cells to thermal ablative injury in a Murine model of colorectal liver metastases. Thermal ablation by laser (Nd-YAG wavelength 1064 nm) was induced in liver and colorectal cancer liver metastases in CBA strain mice. Laser energy was applied at 2 W for 50 s and produced incomplete tumour ablation. Established tissue injury was assessed in separate groups of animals at time points ranging from 12 h to 21 days following therapy. HSP70 and Kupffer cell expression at the margins of coagulated tissue was determined by immunohistochemical staining for HSP70 and F4/80 antigens, respectively. HSP70 was faintly expressed in the cytoplasm of all tumour cells, with distinct clusters exhibiting intense cytoplasmic and nuclear HSP70 staining (130 ± 19 cells mm−2). Comparatively, HSP70 expression was uncommon in untreated control liver specimens (2 ± 2 cells mm−2, p < 0.001). Thermal ablation increased expression of HSP70 at coagulated tissue margins. The peak response in tumours occurred at 2 days post-ablation and was significantly greater than the peak response in liver, occurring at 12 h (809 ± 80 cells mm−2 vs. 454 ± 52 cells mm−2, p < 0.001). HSP70 expression remained significantly elevated for 7 days following therapy in tumour tissue, compared to 3 days in liver. Kupffer cell numbers in untreated control tumours were significantly lower than in untreated control livers (285 ± 23 cells mm−2 vs. 451 ± 30 cells mm−2, p < 0.001). Following thermal ablation, there was an initial decrease in Kupffer cell numbers at the margin of coagulation with subsequent persistent increases thereafter. In liver tissue, the peak Kupffer cell response occurred at 5 days post-therapy and was significantly greater than the peak response in tumour tissue 3 days post-thermal ablation (1074 ± 34 cells mm−2 vs. 860 ± 53 cells mm−2, p = 0.007). Thermal ablation produces a greater and more prolonged HSP70 response in colorectal liver metastases than in liver tissue. It also induces persistent increases in Kupffer cell activity in liver and tumour tissue.

Chondrocutaneous Advancement Flap for Helical Defects-A Case Report Using the Antia-Buch Procedure

The ear is a complex structure with its unique anatomy. Defects caused by tumor ablation and traumatic injuries pose great challenges to the surgeon because a variety of options are available to reconstruct the disfigured ear. The task requires not only a through knowledge of the ear's anatomy but also a sound surgical technique so that a natural and aesthetically appealing ear may be created. However, only a few methods are appropriate for each particular defect. The method chosen is based on the defect size and the availability of the remaining local skin. Several options have been proposed for the reconstruction of the upper third defects. Of these options, the Antia-Buch chondrocutaneous advancement flap is adequate for small helical rim defects. Here we present a case with a marginal defect of the upper third of the helix of a patient's left ear in which the chondrocutaneous advancement flap of Antia and Buch was utilized to cover the defect. The result was acceptable and the satisfaction of the patient was reached. Other methods of reconstruction for deformed ear of this category are put into discussion to justify our choice of the Antia and Buch procedure for the defect of this case.

Regulation of nestin expression after cortical ablation in adult rat brain

During embryogenesis, transient expression of nestin in proliferating neuroepithelial stem cells signals the commitment of progenitor cells to differentiate. Although adult mammalian brain contains very little nestin, significant upregulation of nestin has been reported following cerebral injury, leading to speculation that nestin may be involved in brain repair. In this study, we assessed the temporal profile of nestin expression following ablation injury of the sensory barrel cortex and investigated the influence of contralateral whisker stimulation on nestin expression. Since the adult mammalian brain contains proliferating neuronal progenitor cells that can be labeled with bromodeoxyuridine (BrdU), we also determined the association of nestin reexpression with BrdU-labeled cells. Nestin reexpression was detected predominantly in the ipsilateral cortex 3 days post-ablation. There was no significant nestin upregulation in the subcortical region. Nestin reexpression was most marked surrounding the lesion, but also extended throughout the entire lateral cortex. Nestin in the ipsilateral cortex subsided by day 7, although perilesional nestin expression was still apparent 28 days post-injury. Western blot analysis of nestin expression 3 days post-ablation confirmed a significant two-fold increase in nestin expression ( p<0.05). Double immunofluorescence labeling demonstrated that the majority of nestin expression occurred in astrocytes. We were unable to detect any colocalization with neuronal makers. However, BrdU-labeled cells, which were readily detected in the subventricular zone prior to injury, were readily detected in the perilesional area 3 days post-ablation, concomitant with nestin in this area. Confocal microscopy detected several BrdU-positive cells expressing nestin. Taken together, the data support a potential role for nestin reexpression in brain repair.

Molecular Mechanisms Controlling the Fibrotic Repair Phenotype in Cornea: Implications for Surgical Outcomes

Incisional or ablation injury to the corneal stroma is repaired by deposition of a fibrotic tissue produced by activated keratocytes, whereas cells lost from the underlying stroma after epithelial abrasion are simply replaced by keratocyte replication without expression of fibrotic markers. The purpose of this study was to investigate mechanisms that determine this differential keratocyte response. A penetrating keratectomy rabbit model was adapted for mice to study the fibrotic repair response. A mouse epithelial abrasion model was applied to study the stromal cell replacement response. A primary rabbit corneal cell culture model and an organotypic culture model were also used. When the epithelium was prevented from resurfacing the cornea after penetrating keratectomy, expression of fibrotic markers was considerably reduced. TGF-beta2 was determined to be a major substance produced by corneal epithelial cells capable of inducing the fibrotic phenotype. In the intact mouse cornea, TGF-beta2 was confined to the uninjured epithelium, but was released into the stroma during fibrotic repair. By contrast, TGF-beta1 was never found in the epithelium. When epithelial cells were cultured on a basement-membrane-like gel or allowed to deposit their own basement membrane in organotypic culture, TGF-beta2 production was reduced. Return of a basement membrane after wounding in vivo correlated with loss of the fibrotic phenotype. In the epithelial debridement injury model in which the basement membrane was left intact, TGF-beta2 remained confined to the corneal epithelium, consistent with the absence of a fibrotic phenotype. These data suggest that integrity of the basement membrane is a deciding factor in determining the regenerative character of corneal repair.

Mycophenolate mofetil prevents arteriolopathy and renal injury in subtotal ablation despite persistent hypertension

Although renal protective effect of interrupting the inflammatory process is well established, it is still controversial if it also prevents the glomerular hemodynamic disturbances that initiate renal injury. We investigated the effects of suppressing inflammation with mycophenolate mofetil (MMF) on glomerular hemodynamics, arteriolar structural changes, and renal histologic injury in rats with subtotal renal ablation Micropuncture studies were performed 30 days after 5/6 nephrectomy in rats untreated and treated with MMF (30 mg/kg/day). Renal histology, immunohistochemistry for lymphocytes, macrophages and inducible nitric oxide synthase (iNOS) expression, as well as afferent arteriolar (AA) morphometry was evaluated. Renal ablation significantly increased proteinuria (6.8 to 82.7 mg/day), mean arterial pressure (MAP) (120 to 166 mm Hg), single-nephron glomerular filtration rate (SNGFR) (34.8 to 56.3 nL/min), glomerular plasma flow (QA) (117.7 to 246.9 nL/min), and glomerular capillary pressure (PGC) (48.9 to 61.0 mm Hg). Afferent resistance (AR), efferent resistance, and ultrafiltration coefficient remained unchanged. Despite persisting arterial hypertension (152 mm Hg), MMF prevented proteinuria (13.3 mg/day), and significantly reduced SNGFR (44.4 nL/min), PGC (49.1 mm Hg), and QA (163.2 nL/min) due to a rise in AR (3.13 vs. 2.18 1010 dyn/sec/cm-5). Glomerular sclerosis, tubulointerstitial damage, lymphocyte and macrophage infiltration, and iNOS expression were significantly reduced by MMF, in addition hypertrophy of AA resistance evaluated by the media/lumen ratio was prevented (P < 0.001). Reduction in proteinuria, SNGFR, QA, and PGC, despite elevated MAP, indicate preservation of AA function. These results suggest that inflammation associated arteriolopathy of AA contributes to glomerular hemodynamic disturbances that participate in the progression of renal disease.

Effects of Endothelial Injury on the Rate of Thrombus Organization in Canine Carotid Arteries Occluded with Microcoils

Thrombus organization in canine carotid arteries occluded with platinum microcoils was studied to determine if endothelial injury created with a Xenon Chloride Excimer Laser (XEL) could acclerate endovascular fibrosis. Ten common carotid artery stumps were created in ten dogs. Each of four stumps were schematically divided into four longitudinally contiguous injury zones (thermal ablation injury, non-ablative injury, proximal and distal non-injury zones) to test the effects of ablative and non-ablative injury and to establish a set of internal controls that would account for proximity to circulating blood at the ostium of the occluded artery. Following XEL irradiation of the endothelium through an arteriotomy, each stump was embolized with microcoils. Four control stumps were subjected to sham laser procedures, and embolized in an identical fashion. Two additional stumps were embolized in the absence of sham surgery. Angiographic, gross and histologic analysis was performed after four weeks. Specimens of freshly clotted whole blood mixed with microcoils were used as an additional control. In irradiated stumps and non-irradiated stumps (sham and embolization only), angiography revealed no evidence of coil compaction or recanalization. In all irradiated stumps the thermal ablation zone contained fibrous tissue and neovascularity without unorganized thrombus. The other zones in the irradiated stumps were indistingnishable from each other and from all zones in the non-irradiated sham stumps, containing primarily unorganized thrombus. Stumps embolized in the absence of sham surgery were filled with material that was grossly and microscopically identical to specimens of freshly clotted whole blood containing microcoils. The results indicate that thermal ablation injury of the endothelium accelerates thrombus organization in canine carotid arteries occluded with platinum microcoils.

Cyclic Stretching of Mesangial Cells Up-Regulates Intercellular Adhesion Molecule-1 and Leukocyte Adherence: A Possible New Mechanism for Glomerulosclerosis

Intraglomerular hypertension is a primary causal factor in the progressive glomerulosclerosis that characterizes diabetic nephropathy or severe renal ablation. However, inflammation of the glomerular mesangium also participates in at least the early phase of these diseases. In glomerulonephritis, where inflammation is thought to be the predominant causal factor, intraglomerular hypertension is also often present. Mesangial cells (MCs) are critical in orchestrating key functions of the glomerulus including extracellular matrix metabolism, cytokine production, and interaction with leukocytes. Because MCs are subject to increased stretching when intraglomerular hypertension is present, and in glomerulonephritis MC/leukocyte interactions seem to be mediated primarily via the up-regulation of intercellular adhesion molecule-1 (ICAM-1), we examine the possibility that cyclic stretching is a stimulus for increased MC ICAM-1 activity. We demonstrate that the normal low levels of MC ICAM-1 mRNA and protein are dramatically up-regulated by even short intervals of cyclic stretch. This effect is dose- and time-dependent, and requires little amplitude and a brief period of elongation for significant induction. Stretch-induced MC ICAM-1 also leads to a marked elevation in phagocytic leukocyte adherence. This stimulated adherence is equal or greater than that induced by the inflammatory cytokine tumor necrosis factor-alpha, whereas an additive effect occurs when both are applied in combination. Our results indicate that stretch-induced ICAM-1 may provide a direct link between hypertension and inflammation in the progression of injury and glomerulosclerosis in diabetes, renal ablation, and other forms of glomerulonephritis.

Expression of nuclear factor kappaB and tumor necrosis factor alpha in the mouse brain after experimental thermal ablation injury.

Nuclear factor kappa B (NFkappaB) participates in the regulation of a diverse range of genes involved in inflammation and acute phase responses. We investigated the expression of the activated form of NFkappaB and tumor necrosis factor alpha (TNFalpha), an inflammatory cytokine, in experimental brain injury. We generated focal brain injury in mice using radiofrequency thermal ablation at the caudate putamen in mice. Intracerebral expression of TNFalpha and the p50 and p65 subunits of NFkappaB were studied using immunohistochemistry at 1, 4, and 8 hours and at 1, 2, 4, 8, 14, and 28 days postinjury. Coagulative necrosis approximately 2 mm in diameter was produced at the site of injury. No immunoreactivity for TNFalpha, NFkappaB p50, or NFkappaB p65 was detected in the injured area in the early phase postinjury. On posttrauma Day 2, however, weak expression of TNFalpha, NFkappaB p50, and NFkappaB p65 was detected in mononuclear cells that infiltrated edematous tissue surrounding the lesion. On posttrauma Days 4 to 8, the expression of TNFalpha, NFkappaB p50, and NFkappaB p65 was prominently increased in infiltrating and proliferating mononuclear cells (macrophages and microglia) and in proliferating reactive astrocytes surrounding the lesion. Nuclear subcellular localization of the expression of NFkappaB p50 and p65 was observed, which indicated that these subunits might be activated in these cells. On posttrauma Day 14, the expression of TNFalpha, NFkappaB p50, and NFkappaB p65 decreased and was limited to mononuclear cells, and it finally disappeared on Day 28. The temporal profiles of TNFalpha, NFkappaB p50, and NFkappaB p65 were closely associated with the occurrence of secondary insults and the tissue-remodeling process in wound healing. These results suggest that TNFalpha, NFkappaB p50, and NFkappaB p65 may play a central role in the injury-induced immune response that leads to secondary insults or wound healing after brain injury. Inappropriate and deregulated activation of NFkappaB in injured brain tissue may be implicated in the development of secondary brain damage.

Expression of Nuclear Factor κB and Tumor Necrosis Factor α in the Mouse Brain after Experimental Thermal Ablation Injury

Expression of Nuclear Factor κB and Tumor Necrosis Factor α in the Mouse Brain after Experimental Thermal Ablation Injury

Chronic methylphenidate treatment enhances water maze performance following traumatic brain injury in rats

Methylphenidate (MPH), a central nervous system stimulant with dopaminergic activity, facilitates neurobehavioral outcome following cortical suction ablation injury, but its potential efficacy following experimental traumatic brain injury (TBI) is unknown. Thus, beginning 24 h after controlled cortical impact injury or sham surgery, male Sprague–Dawley rats were injected (i.p.) once daily for 18 days with either MPH (5 mg/kg) or saline vehicle (VEH) and motor function assessed on post-operative days 1–4, followed by Morris water maze training to find a hidden platform on days 14–18. The MPH treatment regimen was ineffective in accelerating beam-balance or beam-walk recovery, but did significantly decrease swim latencies when compared to VEH-treated controls. The results are consistent with published studies showing improved outcome with MPH therapy. Furthermore, this positive finding with delayed treatment suggests that strategies that enhance catecholamine neurotransmission during the chronic post injury phase may be a useful adjunct in ameliorating some of the neurobehavioral sequelae following TBI in humans.

L-DOPS-Accelerated recovery of locomotor function in rats subjected to sensorimotor cortex ablation injury: pharmacobehavioral studies.

Central norepinephrine (NE) has been shown to play a beneficial role in amphetamine-facilitated recovery of behavior. To give insight into understanding the mechanism, the present studies were conducted to examine (a) the effects of L-threo-3,4-dihydroxyphenylserine (L-DOPS) combined with benserazide (BSZ; a peripheral aromatic amino acid decarboxylase inhibitor) and L-3,4-dihydroxyphenylalanine (L-DOPA), precursors of NE and dopamine (DA), respectively, on the recovery from beam-walking performance deficits in rats subjected to unilateral sensorimotor cortex ablation injury, and (b) the relationships between the behavioral recovery and the frequency of postoperative training and the size of ablation injury. It was found that the combined treatments with L-DOPS and BSZ promoted the recovery of locomotor function as early as 24 hours after injury. L-DOPA alone, however, did not facilitate behavioral recovery. The results of assay for the tissue levels of NE and its major metabolite (3-methoxy-4-hydoxyphenylethylene glycol; MHPG) in the brain using high-pressure liquid chromotography showed MHPG, but not NE, significantly increased in the cerebellum and the hippocampus. The behavioral recovery was also significantly correlated with the frequency of training subsequent to injury, but inversely with the size of cortex ablation. These results suggest that NE is likely to modulate functional recovery in this rodent model.