Subsequent Functional Recovery Research Articles

Return to Play Following Sports-Related Mild Traumatic Brain Injury: The Role for Neuropsychology

Cerebral concussions frequently occur at all levels of athletic competition. The effects from these concussions can be transient or may lead to chronic, debilitating symptoms. A growing literature has established that neuropsychological tests are useful in detecting the subtle neurocognitive changes that occur following concussions. The identification of these deficits and subsequent recovery of function can be important components in making return-to-play (RTP) decisions. This article describes the emergence of neuropsychology in sports medicine, discusses the context in which RTP decisions are made, outlines factors that are important to RTP decisions, and presents a model that views the RTP decision as a dynamic risk-benefit analysis that involves complex interactions among variables. It is argued that neuropsychology has a unique, but not exclusive, role in the decision making process. Implications for future research are discussed.

Usefulness of quantitative echocardiographic techniques to predict recovery of regional and global left ventricular function after acute myocardial infarction

The left ventricular response to dobutamine may be quantified using tissue Doppler measurement of myocardial velocity or displacement or 3-dimensional echocardiography to measure ventricular volume and ejection fraction. This study sought to explore the accuracy of these methods for predicting segmental and global responses to therapy. Standard dobutamine and 3-dimensional echocardiography were performed in 92 consecutive patients with abnormal left ventricular function at rest. Recovery of function was defined by comparison with follow-up echocardiography at rest 5 months later. Segments that showed improved regional function at follow-up showed a higher increment in peak tissue Doppler velocity with dobutamine therapy than in nonviable segments (1.2 ± 0.4 vs 0.3 ± 0.2 cm/s, p = 0.001). Similarly, patients who showed a >5% improvement of ejection fraction at follow-up showed a greater displacement response to dobutamine (6.9 ± 3.2 vs 2.1 ± 2.3 mm, p = 0.001), as well as a higher rate of ejection fraction response to dobutamine (9 ± 3% vs 2 ± 2%, p = 0.001). The optimal cutoff values for predicting subsequent recovery of function at rest were an increment of peak velocity >1 cm/s, >5 mm of displacement, and a >5% improvement of ejection fraction with low-dose dobutamine.

Activating Influences on Supporting Cell Proliferation in the Regenerating Avian Cochlea

Aminoglycoside treatment is associated with hair cell death and hearing loss. In the avian inner ear, it has been well-documented that this hair cell death stimulates the proliferation of adjacent supporting cells, leads to a structural regeneration of hair cells, and results in a subsequent recovery of auditory function. We have been studying the mechanisms that lead to hair cell death in the avian cochlea following aminoglycoside treatment and how this process reactivates the cell cycle in a normally quiescent population of supporting cells. Hair cell death appears to be caused by the induction of apoptosis, or programmed cell death. This apoptotic pathway is initiated within the first 12 hours after a single systemic injection of gentamicin (300 mg/kg), as identified by the nuclear-to-cytoplasmic translocation of the T cell-restricted intracellular antigen-related protein (TIAR). TIAR is an RNA binding protein that is normally found in the cell nucleus but that has been shown to exhibit increased cytoplasmic localization in a variety of tissues undergoing apoptosis. Confocal microscopy demonstrated that within 12 hours of gentamicin injection, punctate cytoplasmic TIAR labeling was seen only in those hair cells in the gentamicin-damaged region of the cochlea that would later proceed to die. Even though these early signs of apoptosis could be detected by 12 hours, signs of structural damage to the hair cells and expression of activated forms of execution stage apoptotic enzymes such as caspase-3 were not seen until 24 to 36 hours after the gentamicin injection. These terminal-stage changes in hair cells were accompanied by an intensification and alteration in the immunocytochemical labeling for myosin VIIa, a hair cell-specific unconventional myosin. The final expulsion of hair cells in the gentamicin-damaged region of the cochlea occurred between 48 and 72 hours after the gentamicin injection and was accompanied by pyknotic and TUNEL-labeled hair cell nuclei. Concurrently, the supporting cells in the damaged region of the cochlea began to enter the S (DNA synthesis) phase of the cell cycle by 65 hours and reached a peak in S phase between 72 and 96 hours. The period of S phase was associated with a loss of connexin43-containing gap junctions between supporting cells in the damaged region of the cochlea. New hair cells were identified in the damaged region by their expression of myosin VIIa at 96 hours. The number of new hair cells increased dramatically by 120 hours and was accompanied by a restoration of connexin43-containing gap junctions between supporting cells in the damaged region of the cochlea. These data reinforce the role of apoptosis in the death of cochlear hair cells after gentamicin treatment and suggest that TIAR, myosin VIIa, and caspase-3 are key components in this apoptotic pathway. Moreover, our data suggest that steps in the hair cell apoptotic pathway directly stimulate supporting cell gap junction disassembly, and this leads to proliferation of a subset of these supporting cells.

Delayed facial palsy after resection of vestibular schwannoma

In this study the authors investigate delayed facial palsy (DFP), which is an underreported phenomenon after surgery for vestibular schwannoma (VS). The authors identified 15 (4.8%) patients from a consecutive series of 314 who underwent surgery for VS between 1988 and 2000, and in whom DFP developed. Delayed facial palsy was defined as a deterioration of facial nerve function from House-Brackmann Grades 1 or 2 more than 3 days postoperatively. All patients underwent intraoperative neurophysiological monitoring of facial nerve function. The average latency of DFP was 10.9 days (range 4-30 days). In six patients (40%) minor deterioration (< or = two House-Brackmann grades) had occurred at a mean of 10.2 days postsurgery, whereas in nine patients (60%) moderate deterioration (> or = three House-Brackmann grades) had occurred at a mean of 11.8 days postoperatively. Five (33%) of 15 patients recovered to Grade 1 of 2 function within 6 weeks of DFP onset. Of the 15 patients with DFP, 14 had completed 1 year of follow up at the time of this study. Twelve (80%) of these 15 patients recovered to Grade 1 or 2 function within 3 months, and 13 (93%) of 14 patients recovered within 1 year. In all cases, stimulation of the seventh cranial nerve on completion of tumor resection revealed the nerve to be intact, both anatomically and functionally, to proximal and distal stimulation at 0.1 mA. A smaller tumor diameter correlated with greater recovery of facial nerve function. There was no correlation between the latency or severity of or recovery from DFP, and the patient's age or sex, the surgical approach, frequency of neurotonic seventh nerve discharges, anatomical relationship of the facial nerve to the tumor, patient's history of tobacco use, or cardiovascular disease. It appears that DFP is an uncommon consequence of surgery for VS. Although excellent recovery of facial nerve function to its original postoperative status nearly always occurs after DFP, the magnitude and time course of the disorder were not predictors for subsequent recovery of facial nerve function.

Functional recovery and dendritic hypertrophy after posterior and complete cingulate lesions on postnatal day 10

Rats received lesions of the posterior cingulate cortex or both the anterior and posterior cingulate cortex (total cingulate), or sham procedures, on postnatal Day 10. As adults, animals were trained in the Morris water task. Both the cingulate lesion groups showed substantial functional recovery relative to our previous studies of adult operates or animals with perinatal cingulate lesions. A Golgi analyis of layer III pyramidal cells in parietal cortex showed an increase in dendritic length in the lesion animals relative to sham controls, which is similar to previous findings for rats with anterior cingulate but not motor or parietal lesions. In addition, there was a partial regeneration of the anterior tissue in the total cingulates, which in some cases extended into the posterior region. This is consistent with earlier findings that anterior cingulate lesions around Day 10 stimulate neurogenesis. It appears that there is something special about the reparative processes and subsequent functional recovery that follow midline neocortical lesions. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 138–146, 2002. DOI 10.1002/dev.10024

Functional recovery and dendritic hypertrophy after posterior and complete cingulate lesions on postnatal day 10

Rats received lesions of the posterior cingulate cortex or both the anterior and posterior cingulate cortex (total cingulate), or sham procedures, on postnatal Day 10. As adults, animals were trained in the Morris water task. Both the cingulate lesion groups showed substantial functional recovery relative to our previous studies of adult operates or animals with perinatal cingulate lesions. A Golgi analyis of layer III pyramidal cells in parietal cortex showed an increase in dendritic length in the lesion animals relative to sham controls, which is similar to previous findings for rats with anterior cingulate but not motor or parietal lesions. In addition, there was a partial regeneration of the anterior tissue in the total cingulates, which in some cases extended into the posterior region. This is consistent with earlier findings that anterior cingulate lesions around Day 10 stimulate neurogenesis. It appears that there is something special about the reparative processes and subsequent functional recovery that follow midline neocortical lesions.

Aetiology, previous menstrual function and patterns of neuro-endocrine disturbance as prognostic indicators in hypothalamic amenorrhoea.

Hypothalamic amenorrhoea (HA) is a syndrome associated with infertility and osteopenia in reproductive-age women. To understand better the natural history of this disorder, 28 women participated in a retrospective, questionnaire-based analysis to elucidate factors associated with spontaneous recovery. 54% of subjects developed HA related to an eating disorder, 21% related to stress +/- weight loss, and 25% without obvious contributing factors (idiopathic). HA associated with a clear precipitant had a better prognosis than idiopathic HA (71 versus 29% recovery; P < 0.05). Reversal of the inciting factor appeared necessary but not sufficient for recovery (83% recovery if factor reversed). Normal menarche occurred in 61% of subjects, oligomenorrhoea in 32%, and primary amenorrhoea in 7%. Oligomenorrhoea and normal menarche showed a trend toward better prognosis than primary amenorrhoea (NS). Compared with controls, 46% of HA patients had decreased frequency of LH pulses, 7% decreased amplitude, 18% decreases in both frequency and amplitude, 18% absent pulses, and 11% normal-appearing pulses. Pulse pattern at baseline did not predict recovery. The aetiology of HA at the time of presentation predicts subsequent recovery of menstrual function. In stress, weight loss, or eating disorder-related HA, rates of recovery exceeded 80% when precipitating factors were reversed. Idiopathic HA may represent a different disorder as recovery rates were <30%.

Anatomical bases of the posterior approach to the brachial plexus for repairing avulsed spinal nerve roots

Avulsion of nerve roots from the cervical spinal cord has always been considered as an untreatable injury, even by surgeons with expertise in this area. However, numerous experimental studies in animals, as well as a human case report, showed that if continuity is restored between the spinal cord and nerve roots, axons from spinal motor neurons can regrow into the peripheral nerve graft with a subsequent recovery of motor function. The posterior subscapular approach, based on the evolution of the posterolateral approach for removal of the first rib, is the only way to expose the entire brachial plexus from C5 to T1 from the ventral and dorsal roots to the distal nerve trunks. The purpose of this study is to investigate the topographic anatomy of the brachial plexus, with particular emphasis on the relationships important to the posterior approach and reimplantation of the ventral rootlets within the cord, either directly or using peripheral nerve grafts. The major advantage of the procedure is the proximal exposure of the plexus, with evaluation of the lesions being excellent (intradural, foraminal and proximal trunks). Reimplantation of ventral roots into the cord is relatively easy from C5 to C7, more difficult for C8 and problematic for T1, whereas reimplantation of dorsal roots into the cord is easy from C5 to T1. The disadvantages of this approach for exposure of the plexus and nerve root avulsion repair are significant: the surgical technical steps are difficult mainly because of the cervical paraspinal muscle mass, which cannot be easily "elevated and retracted" despite previous descriptions; bleeding from the venous plexus can be excessive as suggested by dissection and our own experience; the stability of the cervical spine may be compromised following extensive laminectomy with total unilateral facetectomy; exposure of the plexus distal to the division of the trunks is difficult; there may be injury to the long thoracic nerve and subsequent winging of the scapula; and pneumothorax. This approach is therefore only applicable in highly selected cases involving multiple avulsed roots with proximal lesions extending as far as the division of the trunks.

The temporal patterns of c-Fos and basic fibroblast growth factor expression following a unilateral anteromedial cortex lesion

Following a unilateral anteromedial cortex lesion, a critical period of 12 h to 6 days exists during which the recovery process is exquisitely vulnerable to manipulation. Certain anti-convulsant drugs, as well as convulsive seizures impede recovery when administered during, but not after, the critical period. The mechanisms underlying these behavioral phenomena have not been delineated. Thus, the present study was designed to determine potential mechanisms underlying and responsible for the critical period. To this end, we measured the immunoreactivity of two important markers of the post-injury response cascade, c-Fos and bFGF, at designated times after a unilateral anteromedial cortex lesion. These temporal patterns of expression in the perilesional cortex and ipsilateral dorsal striatum were mapped onto functional recovery patterns. Within the critical period, c-Fos was dramatically elevated through 48 h after the lesion, while bFGF peaked later, on day 6. Upregulation of these markers preceded recovery from somatosensory deficits, which was most dramatic after post-operative day 9 and complete by day 23. Early post-lesion expression of c-Fos may contribute to lesion-induced bFGF expression, which through its neurotrophic properties could be responsible for subsequent functional recovery. Gaining a similar understanding of the critical period following human traumatic brain injury could be an important first step toward improved treatment strategies and neurobehavioral outcome.

A longitudinal, functional study of peripheral nerve recovery in the mouse.

To verify the validity of the recently described sciatic functional index for mice to monitor neuronal functional recovery over time using a blinded, randomized, and controlled evaluation. Surgery was performed on the left sciatic nerves of 62 C57/BL mice after randomly assigning them to one of four surgical groups: sham surgery, sciatic nerve crush, nerve transection without repair, and nerve transection followed by epineurial suture repair. Sciatic functional indices were measured before surgery and then after surgery at 10-day intervals for 90 days, using a previously described formula. Sham surgery did not affect nerve function when compared with preoperative values (P > .24). Crush surgery produced a reversible nerve injury that fully recovered after 20 days. Nerve transection without repair resulted in complete functional disability without recovery of function during the 90-day follow-up interval. When transected nerves were repaired, complete functional disability was noted at day 10, with subsequent functional recovery to 26% of function at day 30. This level of recovery persisted until the 60th postoperative day when muscle contractures resulted in progressive worsening of the index. There were statistically significant differences between the sciatic functional indices of each of the groups (P < .05). The previously described sciatic functional index for mice is an accurate indicator of the level of sciatic neuronal function during recovery. This index represents a method of evaluating neuronal function that may provide a better reflection of the recovery parameters that are important in clinical situations. The sciatic functional index will allow for study of sciatic nerve functional recovery in genetically engineered transgenic mice.

Norepinephrine and traumatic brain injury: a possible role in post-traumatic edema

Unilateral cerebral contusion is associated with an early (30 min) increase in norepinephrine (NE) turnover followed by a later (6–24 h) depression of turnover which is bilateral and widespread throughout the brain. Blockade of NE function during the first few hours after traumatic brain injury (TBI) impedes subsequent recovery of function without enlarging the size of the lesion. The current studies were carried out to characterize further the timing of the switch from increased to decreased NE turnover and to investigate the pathogenesis of the delayed recovery of function associated with blocking NE function. Adult male rats had unilateral somatosensory cortex contusions made with a 5 mm diameter impact piston. They were killed after 2 h and their brains analyzed for NE turnover by HPLC with electrochemical detection. In general, NE turnover (the ratio of 3-methoxy-4-hyroxyphenylglycol to NE levels) had returned to sham-lesion control levels in most brain regions by 2 h after either left or right sided contusions. The only exceptions were a persistent 87% increase at the lesion site after right-sided contusions and 22% and 32% increases in the contralateral cerebellum after right- and left-sided contusions, respectively. Blockade of α 1-adrenoceptors by treatment with prazosin (3 mg/ kg, i.p.) 30 min prior to TBI produced edema in the striatum and hippocampus at 24 h which was not seen saline-treated rats nor in rats where NE reuptake was blocked with desmethylimipramine (DMI; 10 mg/kg, i.p.). DMI increased edema at the lesion site at 24 h, however. These data suggest that the early increase in NE release following unilateral cerebral contusion is protective and that this may act to stabilize the blood–brain barrier in areas adjacent to the injury site. Drugs that interfere with this enhanced noradrenergic function might enhance the damage caused by TBI.

Superiority of C-11 acetate compared with F-18 fluorodeoxyglucose in predicting myocardial functional recovery by positron emission tomography in patients with acute myocardial infarction

In patients with chronic coronary artery disease, preservation of myocardial oxidative metabolism measured by positron emission tomography (PET) with 11C-acetate is a more accurate predictor of subsequent myocardial functional recovery than is maintenance of glucose metabolism estimated with 18F-fluorodeoxyglucose. However, whether measurements of myocardial oxidative metabolism are more accurate than measurements of glucose metabolism in predicting functional recovery in patients with recent myocardial infarction is unknown. Myocardial oxidative metabolism was measured within 10 days of infarction in 19 patients by analysis of the rate of myocardial clearance of 11C-acetate. Metabolism of glucose was assessed by analysis of the uptake of 18F-fluorodeoxyglucose. Criteria for prediction of the recovery of function based on measurements of oxidative metabolism and glucose metabolism were compared. Threshold criteria with 11C-acetate exhibited superior positive and negative predictive values (89% and 73%, respectively) compared with the criteria of 18F-fluorodeoxyglucose (65% and 57%, respectively) (p < 0.025). In addition, the magnitude of functional recovery after revascularization correlated with the severity of the metabolic abnormality present initially. In patients with recent myocardial infarction, the extent of functional recovery can be predicted accurately by measurement of regional oxidative metabolism by PET with 11C-acetate, and these measurements are superior to those of 18fluorodeoxyglucose.

Preconditioning

Preconditioning

Hypertonic environment prevents depolarization and improves functional recovery from hypoxia in hippocampal slices.

Treatments that postpone hypoxic spreading depression (SD)-like depolarization (also called anoxic depolarization) facilitate recovery of function after transient cerebral hypoxia. Hypertonia reduces cerebral excitability, and we tested whether it also offers protection against SD-like depolarization and hypoxia. Oxygen was withdrawn from hippocampal slices bathed in normal artificial cerebrospinal fluid (ACSF) and, simultaneously, from slices cut from the same hippocampus but bathed in strongly hypertonic ACSF. Extracellular osmolarity (pi(o)) was increased by adding 100 mM mannitol or fructose to ACSF. Slices in normal pi(o) underwent SD-like negative extracellular voltage shift (delta Vo). The hypertonic slices usually showed no SD-like delta Vo but only a small, gradual negative voltage shift. Hypertonia also prevented the precipitate drop of interstitial calcium level ([Ca2+]o). When oxygenation and normal osmolarity were restored, synaptic transmission in the previously hypertonic slices recovered completely, but 3 h after reoxygenation orthodromically transmitted population spikes of the control slices recovered only 25.1% of the initial control amplitude. We conclude that hypertonic treatment during hypoxia improves subsequent recovery of synaptic function. The protection is probably due to the prevention of calcium uptake by blocking the SD-like depolarization, with the prevention of hypoxic cell swelling playing a lesser role.

Environmentally induced changes in peripheral benzodiazepine receptors are stressor and tissue specific

The stress-induced changes in peripheral benzodiazepine receptors (PBR) can be observed in a number of different tissues, depending upon the nature and chronicity of the aversive experience. In addition, virtually all stress procedures that cause rapid changes in PBR simultaneously increase the physical activity or metabolic rate of the subjects. The present study analyzed the contributions of rapid alterations in activity or metabolic rate with and without aversive stimulation and their subsequent impact on PBR. Mechanically induced increases in activity by forced running stress results in a significant reduction in [ 3H]Ro 5-4864 binding to PBR in olfactory bulb, opposite to the PBR changes in this tissue following forced cold-water swim stress. Pharmacological induction of increased locomotor activity as well as metabolic rate by d-amphetamine causes a significant increase in cardiac PBR binding, again, opposite to the response typically observed following inescapable shock stress. Finally, administration of the anxiogenic beta-carboline, FG-7142, causes increases in both hippocampus and adrenal gland PBR binding reminiscent of acute noise stress exposure. These experiments demonstrate that increased locomotor activity or metabolic rate alone is not a necessary and sufficient condition for previous stress-induced changes in PBR. Conversely, increased metabolic rate coupled with an aversive stimulus appears to be an important factor for inducing stress-like changes in PBR. This data, coupled with previous reports, suggests that rapid alterations in these sites are Stressor and tissue dependent. Finally, we propose that the PBR may be involved in many aspects of the stress response including: a) a biowarning system in adrenal gland, b) participation in stress-induced hypertension via renal PBR, and c) a modulator of stress-induced immunosuppression and subsequent recovery of function or recuperation by actions on immune cells.

788-5 Does Abnormal Recovery of Skeletal Muscle Contribute to Fatigue During Repetitive Activities in CHF?

We have previously shown that skeletal muscle endurance and early (5 minutes) recovery of muscle function are impaired in CHF. Since abnormal muscle recovery could explain the fatigue commonly experienced by CHF patients during repetitive activities, the present study examined whether subsequent recovery of muscle function is prolonged and whether this is associated with impaired recovery of submaximal exercise capacity. 18 class I–IV CHF patients (peak VO 2 16 ± 1 ml/kg/min) and 10 age-matched sedentary controls (CON, peak VO 2 26 ± 1) underwent serial 9-min self-powered treadmill tests and evaluations of quadriceps function over a 24 hr period. Muscle function was assessed by measurements of maximum voluntary contraction force (MVC in ft-Ibs). work during 25 knee extensions (WORK in ft-Ibs), and endurance ratio (ER, the ratio of average peak torque during final 3 to initial 3 repetitions) using an isokinetic dynamometer at baseline and after 10 min, 30 min, 1 hr, 3 hr and 24 hr. Distance walked in 9 min (DIS in m) was measured at baseline and after 30 min, 1 hr, 3 hr and 24 hr. At baseline, CHF patients walked less far (367 ± 32 vs 667 ± 27 m, p &lt; 0.001) and performed less knee extensor work (1075 ± 116 vs 1390 ± 110 ft-Ibs, P &lt; 0.05) than controls. MVC and ER also trended lower in CHF patients (80 ± 4 vs 90 ± 6 ft-Ibs, p = 0.15, and 0.51 ± 0,03 vs 0.58 ± 0.02, P = 0.11, respectively. Although DIS and WORK remained significantly lower in CHF patients at each subsequent time point, there was complete recovery to baseline values in both groups by the first repeat measurement. As compared to baseline, the DIS walked on subsequent tests ranged from 99–108% and 100–102% of baseline in CHF patients and controls, respectively. Similarly, WORK ranged from 93–103%, and 99–105% of baseline, MVCfrom 97–106% and 95–104%, and ER from 98–119% and 108–117%, in patients and controls, respectively. Therefore, we conclude that the fatigue experienced during daily activities by CHF patients is not due to impaired recovery of muscle function and is not manifested as a delay in the recovery of submaximal exercise capacity.

Peripheral nerve repair with nerve growth factor and fibrin matrix

A fibrin sealant matrix (FS) with or without a nerve growth factor (NGF) has been used to improve the recovery of severed peripheral nerves, and these have been compared with the results of using only the standard epineural suture (SUT). Regeneration in the early phase (up to 6 days) was measured by the pinch test. The functional recovery process (up to 12 weeks) was evaluated by serial gait track analysis. Longitudinal sections of the nerve specimens were submitted to immunohistochemical staining with monoclonal antibody against neurofilament. In addition, the release of the NGF from the NGF-FS matrix in vitro was investigated by ELISA. The regeneration of the leading sensory fibers was significantly faster in both FS groups (with and without NGF) than in the SUT group at 3 and 4 days postoperatively. The behavioural data expressed by the sciatic function index (SFI) and the toe spreading index (TSI) indicated significant improvement in NGF-FS group at the 9th week postoperatively (p<0.05). Histologically, good and excellent outgrowth of neurites was encountered in both the NGF-FS and FS groups, while most of the results from SUT group were poor to satisfactory. In vitro, a peak of NGF release was seen within 18 h; afterwards, release remained slow for two weeks. It has been concluded that local application of a combination of FS and NGF may be useful for neuritic regeneration and subsequent functional recovery; the fibrin matrix itself may be beneficial for neuritic sprouting in the early phase.

Induction of fetal demise in advanced pregnancy terminations: report on a funic potassium chloride protocol.

Advanced pregnancy termination with uterotonic agents with their inherent risk for occurrence of a live birth and surgical evacuation of a fetus perceived to be vigorous can both be sources of emotional anguish for women. They argue for offering women an option for induction of fetal demise prior to uterine evacuation. We report on our experience with 60 pregnancies in which lethal fetal administration of potassium chloride was performed prior to evacuation of the uterus. We describe a double-bolus technique for funic intravascular injection of potassium chloride to arrest the fetal heart. There were no maternal complications and the procedure was successful in 86.7% (n = 52) of the cases; of the remaining 8 cases, 7 had demise induced by direct fetal cardiac injection, and a live birth occurred in 1 case.

Consequences of Spinal Cord Injury during the Neonatal Period on Micturition Reflexes in the Rat

This study examined the changes in micturition reflexes following spinal cord transection in neonatal rats to determine: (1) whether injury to the immature nervous system allows greater recovery of function than injury in adult animals and (2) whether the management of the lower urinary tract during the initial period following spinal injury influences the subsequent recovery of function. In one experiment, bladder-to-bladder reflexes in decerebrate neonatal rats (Day 15-Day 26) were tested 5-11 days after T8-T10 spinalization. While there was no difference in the amplitude and duration of reflex bladder contractions or bladder capacity between these pups and their nonspinalized controls, the spinalized pups exhibited incomplete voiding and an uncoordinated urethral sphincter (bladder/ sphincter dyssynergia). It is concluded that the dyssynergia is inherent to the spinal micturition reflexes and is not due to an initial period of bladder areflexia and overdistension since in both the control and spinalized neonates micturition is initiated by a somatobladder reflex triggered when the mother licks the perineum. A second experiment tested whether neonatal spinal cord injury led to improved bladder function in adulthood. Postnatal Day 1 rat pups were spinalized at T8-T10 and returned to their mothers for the remainder of the neonatal period, and their bladder reflexes were tested 4-6 months later under urethane anesthesia. These rats showed the same lower urinary tract dysfunctions (bladder/sphincter dyssynergia, high residual volumes, decreased percentage voided volumes, and large-amplitude, long-duration bladder contractions) as adult rats that were spinalized as adults. It is concluded that spinal cord injury in neonates and adult animals leads to a similar disruption of voiding reflexes.

Recovery of Contractile Function of Postischemic, Reperfused Myocardium

Inhibition of mechanical activity during ischemia could improve recovery of stunned myocardium. In this study, the effect of 2,3-butanedione-2-monoxime (BDM), an agent that disrupts excitation-contraction coupling, on the time course of recovery of contractile function of postischemic reperfused myocardium was studied in open-chest anesthetized dogs. Ischemia was produced by occluding the left anterior descending coronary artery (LAD) for 15 mins. In separate experimental groups, during the occlusion period, 6 ml of either 100 mM BDM or drug vehicle (0.9% normal saline) was infused into the distal perfusion bed subjected to occlusion. Regional myocardial function (percentages of segment shortening % SS) was assessed by sonomicrometry. LAD occlusion resulted in similar degrees of dyskinesia in both experimental groups. Subsequent recovery of contractile function during reperfusion was evaluated for 3 h. In control experiments, segment shortening remained significantly (p < 0.05) decreased throughout the reperfusion period, returning to only 36.1 +/- 9.2% of the preocclusion value at 3 h postreperfusion. In BDM experiments, regional contractile function returned to 72.4 +/- 11.3% of the preocclusion value at 1 h of reperfusion. Rapid recovery was sustained throughout reperfusion. Regional stroke work area (RSWA) also demonstrated rapid sustained recovery of function after treatment with BDM. RSWA was significantly greater in BDM experiments as compared with control experiments at all times during the reperfusion period. These results demonstrate that selective intracoronary (i.c.) administration of BDM during ischemia markedly enhances postischemic recovery of contractile function. The underlying mechanism for this action may involve modulation of several aspects of impaired cellular function in postischemic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)