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Use of percutaneous endoscopic gastrostomy feeding tubes and functional recovery in stroke rehabilitation: a case-matched controlled study.

OBJECTIVE: To compare the morbidity, mortality, and functional recovery of patients who require percutaneous endoscopic gastrostomy (PEG) placement for the management of dysphagia after stroke. DESIGN: Retrospective case-matched controlled study. SETTING: Acute stroke rehabilitation inpatient unit. PARTICIPANTS: Patients (N=193) who were admitted for stroke rehabilitation with a PEG tube in place from January 1, 1993, to December 31, 2002, were matched with 193 case controls without PEG. Patients and controls were within 90 days of stroke onset, and were matched for age, sex, type of stroke, FIM instrument score, duration from onset to stroke unit admission, and year of admission. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Length of rehabilitation hospital stay, improvement in FIM scores, FIM efficiency score, need for transfer back to acute care hospital, diagnosis for which transfer was required, final discharge destination, and survival status. RESULTS: Significant differences were found between the 2 groups, PEG versus control, respectively, in the following variables: FIM efficiency (.42+/-.57 vs .56+/-.55, P =.016); need for transfer back to acute hospital (58/193 vs 23/193, P =.001); and survival status dead/alive (14/179 vs 3/190, P =.006). Nonsignificant differences were as follows: length of rehabilitation hospital stay (46.9+/-24.8d vs 43.3+/-19.7d, P =.11), improvement in total FIM score from admission to discharge (16.9+/-17.9 vs 21.0+/-15.5, P =.72), and final discharge destination home/institutional care (96/83 vs 101/89, P =.93). Pneumonia was the most frequent reason for transfer to acute care for patients with PEG. CONCLUSIONS: Patients who meet criteria for admission to a stroke rehabilitation unit and who have a PEG in place are at increased risk for medical complications and death. Those who survive, however, show similar functional recovery and rate of home discharge as case-matched controls.

Aged↗

The effect of the ultrashort beta-blocker esmolol on cardiac function recovery: an experimental study.

OBJECTIVE: This is an experimental work designed to determine, using the isolated perfused rat heart, the effect of the ultra-short acting beta-blocker esmolol on cardiac arrest and cardiac function recovery following esmolol withdrawal. METHODS: Changes in heart rate, coronary flow, diastolic pressure and the rate pressure product were evaluated on the isolated heart (Langendorff model). Esmolol concentrations of 125, 250, and 500 mg/l were tested. In another experiment using esmolol concentration of 250 mg/l, cardiac function recovery was assessed after 20- and 45-min arrest. RESULTS: While concentrations of 250 and 500 mg/l are necessary to produce cardiac arrest, the concentration of 500 mg/l does not result in full cardiac function recovery following esmolol withdrawal. After the highest concentration of esmolol, coronary flow, heart rate and the rate-pressure product recovered to about 80, 70 and 60% of the initial control values, respectively. When comparing 20- and 45-min arrests we found cardiac function normalization occurs later after 45-min arrest. CONCLUSION: The induction of cardiac arrest by esmolol is optimal at a concentration of 250 mg/l. A concentration of 125 mg/l does not result in cardiac arrest and produces bradycardia only, a concentration of 500 mg/l may be dangerous on account of persisting undesirable effects on the rat heart.

Adrenergic beta-Antagonists↗

Functional recovery and enhanced corticofugal plasticity after unilateral pyramidal tract lesion and blockade of myelin-associated neurite growth inhibitors in adult rats.

After a lesion of the mature CNS, structural plasticity and functional recovery are very limited, in contrast to the developing CNS. The postnatal decrease in plasticity is correlated in time with the formation of myelin. To investigate the possible role of an important myelin-associated neurite growth inhibitor (NI-250; IN-1 antigen), one pyramidal tract of adult Lewis rats was lesioned (pyramidotomy), and the rats were treated with the antibody IN-1, a control antibody, or no antibody. Functional recovery was studied from postoperative day 14 until day 42 using a food pellet reaching task, rope climbing, and a grid walk paradigm. The corticofugal projections to the red nucleus and basilar pontine nuclei were analyzed after survival times of 2 and 16 weeks. Treatment with the monoclonal antibody IN-1 resulted in almost complete restoration of skilled forelimb use, whereas all the control groups showed severe and chronic impairments. This functional recovery was paralleled by sprouting of the corticorubral and the corticopontine fibers across the midline, thus establishing a bilateral, anatomically specific projection.

Animals↗

Subcortical vascular lesions and functional recovery in older patients with gait disorders.

This study aimed to assess whether subcortical vascular lesions (SVLs) predict functional recovery after rehabilitation in elderly patients with gait disorders (GD) due to multiple etiology (GD-ME). All patients consecutively admitted with GD-ME (n=103) in our Rehabilitation and Aged Care Unit (RACU) underwent a standardized rehabilitative program. The outcome measure was the Barthel Index (BI) Relative Functional Gain (RFG), a measure of improvement adjusting for baseline functional level. Potential predictors included cognition, depression, functional and nutritional status, physical health, occurrence of adverse clinical events during hospital stay, and SVLs, assessed with a validated visual rating scale based on brain CT scans. Predictors were divided into quartiles and the association with RFG was assessed. In a multivariate linear regression model, SVLs maintained its predictive power on RFG after adjustment for age, gender, and adverse clinical events, which was the only variable associated to RFG in the bivariate model (adjusted p=0.002 for trend). The study shows that SVLs is a predictor of functional recovery in elderly patients with GD-ME.

Aged↗

Degradation of chondroitin sulfate proteoglycans potentiates transplant-mediated axonal remodeling and functional recovery after spinal cord injury in adult rats.

Transplantation of growth-permissive cells or tissues was used to bridge a lesion cavity and induce axonal growth in experimental spinal cord injury (SCI). Axonal interactions between host and transplant may be affected by upregulation of inhibitory chondroitin sulfate proteoglycans (CSPGs) following various transplantation strategies. The extent of axonal growth and functional recovery after transplantation of embryonic spinal cord tissue decreases in adult compared to neonatal host. We hypothesized that CSPGs contribute to the decrease in the extent to which transplant supports axonal remodeling and functional recovery. Expression of CSPGs increased after overhemisection SCI in adult rats but not in neonates. Embryonic spinal cord transplant was surrounded by CSPGs deposited in host cord, and the interface between host and transplant seemed to contain a large amount of CSPGs. Intrathecally delivered chondroitinase ABC (C'ase) improved recovery of distal forelimb usage and skilled motor behavior after C4 overhemisection injury and transplantation in adults. This behavioral recovery was accompanied by an increased amount of raphespinal axons growing into the transplant, and raphespinal innervation to the cervical motor region was promoted by C'ase plus transplant. Moreover, C'ase increased the number of transplanted neurons that grew axons to the host cervical enlargement, suggesting that degradation of CSPGs supports remodeling not only of host axons but also axons from transplanted neurons. Our results suggest that CSPGs constitute an inhibitory barrier to prevent axonal interactions between host and transplant in adults, and degradation of the inhibitory barrier can potentiate transplant-mediated axonal remodeling and functional recovery after SCI.

Animals↗

Comparison of baseline and low-dose dobutamine technetium-99m sestamibi scintigraphy with low-dose dobutamine echocardiography for predicting functional recovery after revascularization.

Injection of sestamibi during low-dose dobutamine (LDD) infusion might improve tracer ability to detect viable myocardium. This study investigated the potential value of LDD technetium-99m sestamibi (sestamibi) single-photon emission computed tomography (SPECT) in predicting functional recovery after revascularization by comparing its results with those of sestamibi SPECT at rest and of LDD echocardiography. Before revascularization, 23 patients with chronic coronary artery disease and regional left ventricular dysfunction underwent sestamibi SPECT at rest and, on a separate day, LDD echocardiography and sestamibi SPECT with tracer injection during LDD infusion. Echocardiography at rest was repeated after revascularization. Semiquantitative sestamibi uptake results (grading from 0 = normal to 4 = absent) and wall motion (grading from 1 = normal to 4 = dyskinesia) were evaluated with a 16-segment model. The ventricular wall was divided into 3 vascular territories. At follow-up, 20 of 32 asynergic vascular territories showed functional recovery, whereas 12 showed no changes. For prediction of functional recovery, LDD SPECT achieved better accuracy than SPECT at rest (87% vs 65%, p <0.05); positive and negative predictive values of LDD SPECT were 90% and 83%, respectively, which was not significantly different from the related LDD echocardiographic values (84% and 69%). Thus, LDD sestamibi SPECT appears to be a promising method for detecting myocardial viability, which provides better accuracy than sestamibi SPECT at rest, and achieves predictive values comparable to those of LDD echocardiography.

Aged↗

Adenosine's effect on myocardial functional recovery: substrate or signal?

During induced ischemia for cardiac surgery, nucleotides are degraded while being used to maintain myocyte integrity. The resulting nucleosides washout upon reperfusion, limiting nucleotide resynthesis resulting in poor postischemic cardiac function. We studied if the mechanism of the beneficial effect of adenosine, a nucleotide precursor, which is known to improve postischemic functional recovery is as a substrate for nucleotide resynthesis or by stimulation of adenosine A1 or A2 receptors. Isolated, retrograde-perfused rabbit hearts received cardioplegia as controls or cardioplegia containing 80 microM [R]-N6-[1-methyl-2-phenylethyl]-adenosine, an A1 receptor agonist, or 200 microM 5'-(N-ethylcarboxamido)adenosine, or 200 microM adenosine alone. To assess functional recovery developed pressure, max dP/dt, pressure-rate product, coronary flow, and myocardial oxygen consumption were compared after 120 min of 34 degrees C global cardioplegic ischemia. Following ischemia and reperfusion, adenosine alone had better developed pressure, dP/dt, and pressure-rate product, while heart rates, wet weights, %H2O, end-diastolic volumes/pressures, and oxygen extraction were not significantly different between groups. While adenosine receptor stimulation may play a role, in this model the beneficial effect of adenosine on functional recovery appears to be mediated more by adenosine's role as a substrate for nucleotide resynthesis.

Adenosine↗

Prediction of functional recovery of 60-minute warm ischemic hearts from asphyxiated canine non-heart-beating donors.

BACKGROUND: Cardiac function of non-heart-beating donors (NHBDs) is uncertain due to severe myocardial damage. We developed an isolated myocardial perfusion system to resuscitate NHBD hearts and attempted to predict functional recovery of 60-minute warm ischemic hearts by analyzing systolic and diastolic functions. METHODS: Hypoxic cardiac arrest was induced in 8 mongrel dogs without any pre-treatments. After 60-minute ischemia, intracoronary microthrombi were flushed out by retrograde blood cardiopledia with tissue-type plasminogen activator. Coronary arteries were initially perfused from the aortic root with tepid hyperkalemic blood (20 mmol/liter) at low pressure (20 mm Hg) for the first 60 minutes and then with normothermic blood for the next 60 minutes. After 120 minutes of reperfusion, pre-load was increased for ejection against an after-load of 80 mm Hg. Pressure-volume loops were recorded to obtain the end-systolic pressure-volume relationship (ESPVR) and end-diastolic pressure-volume relationship (EDPVR). Stroke volume at a given pre-load was calculated from averaged ESPVR, EDPVR and after-load identical to an averaged baseline value. The Frank-Starling relationship was obtained and cardiac status was classified according to Forrester's hemodynamic sub-set. RESULTS: End-systolic elastance decreased significantly to about 60% of baseline and the time constant of isovolumic relaxation was prolonged significantly by about 20%. Cardiac index was decreased to about 50% and cardiac status was classified in the Forrester III or IV sub-set. CONCLUSIONS: The extent of functional recovery of NHBD hearts is predictable by cardiac output. Although 120 minutes of recovery time may be short for 60-minute ischemic damage, this system may be feasible to predict post-transplant cardiac function before transplantation.

Animals↗

The rate of functional recovery from acute IOP elevation.

PURPOSE: To evaluate the recovery of retinal function after acute IOP elevation. METHODS: The electroretinogram (ERG) was measured before, during, and after IOP increased to 50 and 70 mm Hg at different durations in anesthetized, dark-adapted rats (n = 5-7). Signals were collected for dim and bright flashes (-4.95 and 1.0 log cd . s/m(2)) and analyzed in terms of the photoreceptoral (P3), postreceptoral (P2), and inner retinal (negative scotopic threshold response [nSTR]) responses. Parameters (treatment/baseline, %) were compared across time by using repeated-measures ANOVA and t-tests. The rate of recovery was quantified with a logistic function and compared by bootstrap. RESULTS: IOP spikes induce greater loss (P < 0.01) and slower recovery (P < 0.001) in the nSTR compared with the P2 and P3 responses. IOP spikes having common integral (pressure x duration, 2100 mm Hg x minutes) for insult gave significantly greater P2 and nSTR dysfunction at the higher pressure (70 vs. 50 mm Hg, nSTR reduced to -2.5% +/- 0.5% vs. 20.3% +/- 6.5%, P < 0.05). The higher pressure also produced significantly slower nSTR recovery (50% recovery time [t(0.5)] 70 vs. 50 mm Hg: 33.1 vs. 21.7 minutes; P < 0.05). At a given IOP (70 mm Hg), t(0.5) showed a linear relationship with duration (15 vs. 30 vs. 60 minutes' exposure: t(0.5) 16.7 vs. 33.1 vs. 63.2 minutes; P < 0.05) and integral. CONCLUSIONS: Ganglion cell function recovers slower than the outer retina after IOP insult, with peak IOP being the principle determinant of functional loss and recovery. For a fixed pressure, functional recovery is linearly related to exposure.

Animals↗

Neuroimmunophilin ligands improve functional recovery and increase axonal growth after spinal cord hemisection in rats.

We have previously shown that FK506 accelerates the rate of nerve regeneration in the peripheral nervous system (PNS) and increases regeneration of central nervous system (CNS) axons into a peripheral nerve graft. In the present study, we examined whether FK506 and a nonimmunosuppressive derivative (FK1706) improve functional recovery and long distance regeneration following a hemisection lesion of spinal cord at T10/T11. Rats were given daily subcutaneous injections of either FK506 (2 mg/kg/day), FK1706 (2 mg/kg/day), an equivalent volume of saline or 30% DMSO as vehicle, respectively. Functional recovery was assessed using a modified Tarlov/Klinger scale, walking along progressively narrower wooden beams (7.7-1.7 cm widths), and analysis of footprints obtained during walking. Compared to both control groups, FK506 and FK1706-treated animals demonstrated significant functional recovery 4 days (beam walking), 2 weeks (footprints), and 4 weeks (Tarlov/Klinger scale). By 11 weeks, FK506-treated and FK1706-treated animals were able to walk, albeit poorly, along even the narrowest (1.7 cm) beam. At 11 weeks, the spinal cords were re-exposed and a small piece of gel foam-soaked Fluoro-Gold was placed on the injured side 2-cm caudal to the first injury. Five days later, the animals were perfused and tissues prepared for fluorescence microscopy. FK506-treated and FK1706-treated rats demonstrate a significantly greater number of retrogradely labeled neurons in the red nucleus. The results implicate a nonimmunosuppressant mechanism in FK506's action and suggest that FK506 or a nonimmunosuppressant derivative may be useful for treatment of spinal cord injuries.

Animals↗

Functional recovery of transected nerves treated with systemic BDNF and CNTF.

The purpose of this study was to investigate the effect of systemic co-injections of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) on the functional recovery of transected sciatic nerves repaired by epineurial coaptation (EC) or collagen tubulization (CT). Forty Sprague-Dawley rats underwent transection of their sciatic nerves and repair by either EC or CT. With each repair technique, systemic injections of neurotrophic factors or control injections of lactated Ringer's solution were given. This resulted in four treatment groups: EC, EC + BDNF/CNTF, CT, and CT + BDNF/CNTF. Nerve function was assessed using sciatic functional indices (SFI). Animals whose nerves were repaired by CT (P = 0.01), CT + BDNF/CNTF (P = 0.04), and EC + BDNF/CNTF (P = 0.04) all had better functional recovery than those whose nerves were repaired by EC. There were no significant differences among these three groups, however. Animals in the CT group manifested the most rapid rate of recovery (P = 0.02 compared with EC). Collagen tubulization and systemic co-injections of BDNF/CNTF improve the rate and extent of sciatic functional recovery after nerve repair. The improvement in recovery conferred is not additive.

Animals↗

Accuracy of currently available techniques for prediction of functional recovery after revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease: comparison of pooled data.

OBJECTIVES: This study evaluated the relative merits of the most frequently used techniques for predicting improvement in regional contractile function after coronary revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease. BACKGROUND: Several techniques have been proposed for predicting improvement in regional contractile function after revascularization, including thallium-201 (Tl-201) stress-redistribution-reinjection, Tl-201 rest-redistribution, fluorine-18 fluorodeoxyglucose with positron emission tomography, technetium-99m sestamibi imaging and low dose dobutamine echocardiography (LDDE). METHODS: A systematic review of all reports on prediction of functional recovery after revascularization in patients with chronic coronary artery disease (published between 1980 and March 1997) revealed 37 with sufficient details for calculating the sensitivity and specificity of each imaging modality. From the pooled data, 95% and 99% confidence intervals were also calculated. RESULTS: Sensitivity for predicting regional functional recovery after revascularization was high for all techniques. The specificity of both Tl-201 protocols was significantly lower (p < 0.05) and LDDE significantly higher (p < 0.01) than that of the other techniques. CONCLUSIONS: Pooled analysis of 37 studies showed that although all techniques accurately identify segments with improved contractile function after revascularization, the Tl-201 protocols may overestimate functional recovery. The evidence available thus far indicates that LDDE appears to have the highest predictive accuracy.

Chronic Disease↗

The effect of human chorionic gonadotropin (HCG) on functional recovery of spinal cord sectioned rats.

The effect of human chorionic gonadotropin (HCG) on functional recovery after complete spinal cord transection in the rat was studied. Twelve rats (6 male and 6 female) received HCG daily for the first week and then every alternate day for three weeks. Ten rats (5 male and 5 female) served as controls. Return of bladder function, Tarlov's grading and measuring the maximum angle at which the rats were able to climb up an inclined plane were used as criteria in assessing the functional recovery. Improvement was noted in the HCG-treated rats by the end of two weeks. At six weeks the recovery of HCG-treated rats as compared to the control group was very significant (p less than 0.001). No recovery whatsoever was noted in the control group even after six weeks. Histological evidence of bridging of the gap between the cut ends of the spinal cord by nerve fibres containing tissue was noted in the HCG-treated rats only. The possible mode of action of HCG on spinal cord injury is briefly discussed.

Animals↗

Functional recovery after traumatic transtentorial herniation.

To elucidate the factors associated with functional recovery after traumatic transtentorial herniation, we reviewed the records of 153 consecutive patients admitted with clinical signs of transtentorial herniation (altered level of consciousness, anisocoria or pupillary unresponsiveness, and abnormal motor findings). Overall, 28 patients (18%) had a functional outcome: 14 patients (9%) made a good recovery and 14 were moderately disabled. Sixteen patients (10.5%) were severely disabled or vegetative, and 104 (60%) died. Compared with patients who died or were left severely disabled or vegetative, patients who had a good recovery were younger (21 versus 38 years), were significantly more likely to be children (less than or equal to 17 years old) and have anisocoria and a deteriorating Glasgow Coma Score (GCS), and were significantly less likely to be flaccid or have bilaterally fixed pupils; moderately disabled patients also had a lower median age and a higher frequency of anisocoria. There was no difference in the incidence of significant intracranial hematomas between patients with a functional outcome and those with a nonfunctional outcome. Twenty-seven percent of the 95 patients with anisocoria had a good outcome or moderate disability, whereas only 3.5% of the 58 patients with bilaterally fixed and dilated pupils at admission had a functional recovery (P less than 0.05). Age, level of consciousness, and the degree of residual upper brain stem function at admission appear to be the most important determinants of functional outcome after traumatic transtentorial herniation.

Adolescent↗

Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death.

The selective cyclooxygenase-2 (COX-2) inhibitor has been reported to have antiinflammatory, neuroprotective, and antioxidant effects in ischemia models. In this study, the authors examined whether a selective COX-2 inhibitor (celecoxib) reduces cerebral inflammation and edema after intracerebral hemorrhage (ICH), and whether functional recovery is sustained with longer treatment. ICH was induced using collagenase in adult rats. Celecoxib (10 or 20 mg/kg) was administered intraperitoneally 20 minutes, 6 hours, and 24 hours after ICH and then daily thereafter. Seventy-two hours after ICH induction, the rats were killed for histologic assessment and measurement of brain edema and prostaglandin E2. Behavioral tests were performed before and 1, 7, 14, 21, and 28 days after ICH. The brain water content of celecoxib-treated rats decreased both in lesioned and nonlesioned hemispheres in a dose-dependent manner. Compared with the ICH-only group, the number of TUNEL-positive, myeloperoxidase-positive, or OX42-positive cells was decreased in the periphery of hematoma and brain prostaglandin E2 level was reduced in the celecoxib-treated group. Celecoxib-treated rats recovered better by the behavioral tests at 7 days after ICH throughout the 28-day period, and the earlier the drug was administered, the better the functional recovery. Evidence of similar effects in an autologous blood-injected model showed that direct collagenase toxicity was not the major cause of inflammation or cell death. These data suggest that celecoxib treatment after ICH reduces prostaglandin E2 production, brain edema, inflammation, and perihematomal cell death in the perihematomal zone and induces better functional recovery.

Animals↗

Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats.

In these studies, we examined the neuroprotective effects of the potent antiinflammatory cytokine interleukin-10 (IL-10) following spinal cord injury (SCI). Neuroprotection was assessed by using behavioral and morphological end points. We hypothesized that injury-induced inflammation contributes to the resulting neuropathology and subsequent loss of function. Therefore, by attenuating injury-induced inflammation, we should promote functional recovery. The New York University device was used to induce moderate SCI and study the resulting inflammatory response and functional consequences of inhibiting this response in rats. We determined that SCI induces the expression of tumor necrosis factor-alpha (TNF-alpha) in the spinal cord and by SCI-activated monocytes isolated from the peripheral circulation. IL-10 (5.0 microg) administered 30 minutes after-injury significantly reduced the expression of TNF-alpha protein in the spinal cord and in vitro by SCI-activated monocytes. Next, we investigated whether IL-10 would improve functional recovery after SCI. Randomized, double-blinded studies demonstrated that a single injection of IL-10 significantly improves hind limb motor function 2 months after injury, as determined by the Basso, Beattie and Bresnahan (BBB) open-field behavioral test. IL-10-treated animals had a mean BBB score of 18.0+/-0.5 (SEM, n = 9) compared with a score of 12.9+/-0.6 (SEM, n = 9) for the saline-treated controls. Morphological analysis demonstrated that IL-10 reduces lesion volume by approximately 49% 2 months after injury. These data suggest that acute administration of IL-10 reduces TNF-alpha synthesis in the spinal cord and by activated macrophages, is neuroprotective, and promotes functional recovery following SCI.

Animals↗

Perflubron emulsion prevents PMN activation and improves myocardial functional recovery after cold ischemia and reperfusion.

BACKGROUND: In cardiopulmonary bypass, extracorporeal circulation activates neutrophils, which contribute to ischemia reperfusion injury and postoperative myocardial dysfunction. Perfluorocarbons (PFCs) are compounds that dissolve oxygen and have anti-inflammatory and neutrophil-stabilizing properties. We hypothesized that perflubron emulsion (PFE), a PFC, would attenuate neutrophil activation during simulated extracorporeal circulation (SECC) and would preserve myocardial functional recovery during reperfusion after cold ischemia. METHODS: In a SECC, diluted blood was circulated for 120 min and subsequently used to reperfuse isolated rat hearts after 2 h of cold (12 degrees C) ischemia. Three groups were studied: noncirculated control; SECC/no additive; and SECC/PFE added. In control and SECC/no additive groups, whole blood was diluted 1:1 with plasmalyte. SECC/PFE blood was diluted 1:1 with plasmalyte and PFE (0.075 mL/mL diluted whole blood). Blood counts and neutrophil activation experiments were performed before and after 120 min of SECC. Reperfusion was accomplished using a modified Langendorff preparation. Left ventricular developed pressure, dP/dt, and coronary flow were measured at 10, 15, and 20 min of reperfusion. RESULTS: After 120 min SECC, neutrophil activation was significantly reduced in the SECC/PFE group compared to the SECC/no additive group (38.1 +/- 2.3% versus 51.7 +/- 1.0%, P < 0.05). Compared to cold ischemic hearts reperfused with fresh, non-recirculated blood, left ventricular developed pressure and dP/dt were significantly impaired in the cold ischemic hearts reperfused with SECC/no additive blood (P < 0.05). In contrast, myocardial functional recovery was not impaired in the hearts reperfused with SECC/PFE blood. CONCLUSIONS: SECC-induced neutrophil activation was attenuated with Perflubron treatment. In addition, the progressive impairment in myocardial functional recovery after cold ischemia was significantly improved with treatment. PFE has clinical potential to limit neutrophil-mediated reperfusion injury following cold ischemia.

Animals↗

Interleukin-6 promotes sprouting and functional recovery in lesioned organotypic hippocampal slice cultures.

Interleukin (IL)-6 is a pro-inflammatory cytokine now widely recognized to contribute to the molecular events that follow CNS injury. Little is known, however, about its action on axonal sprouting and regeneration in the brain. We addressed this issue using the model of transection of Schaffer collaterals in mice organotypic hippocampal slice cultures. Transection of slice cultures was associated with a marked release of IL-6 that could be neutralized by an IL-6 blocking antibody. We monitored functional recovery across the lesion by recording synaptic responses using a multi-electrode array. We found that application of IL-6 antibodies to the cultures after lesioning significantly reduced functional recovery across the lesion. Furthermore, the level of expression of the 43-kDa growth-associated protein (GAP-43) was lower in slices treated with the IL-6 neutralizing antibody than in those treated with a control IgG. Conversely, addition of exogenous IL-6 to the culture medium resulted in a dose-dependent enhancement of functional recovery across the lesion and a higher level of expression of GAP-43. Co-culture of CA3 hemi-slices from thy1-YFP mice with CA1 hemi-slices from wild-type animals confirmed that IL-6-treated co-cultures exhibited an increased number of growing fluorescent fibres across the lesion site. Taken together these data indicate that IL-6 plays an important role in CNS repair mechanisms by promoting regrowth and axon regeneration.

Animals↗