Serial Lesion Research Articles

Relationship Between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute TBI Patients: an Exploratory Analysis

BackgroundFailure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI.MethodsWe conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses.ResultsWe observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status.ConclusionsOur preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.

Fractional Flow Reserve Assessment of a Significant Coronary Stenosis Masked by a Downstream Serial Lesion.

Fractional flow reserve (FFR) has been recognized as an effective tool to determine functional significance in intermediate coronary lesions and FFR-guided percutaneous coronary intervention (PCI) improves clinical outcomes. However, hemodynamic interaction between serial stenoses within one coronary artery complicates the assessment of functional severity of each individual lesion. We present a case in which FFR measurement by intracoronary bolus injection of adenosine helps to make appropriate revascularization decision in serial stenoses when the procedures are performed systemically and properly.

Successive bilateral frontal controlled cortical impact injuries show behavioral savings

Traumatic brain injuries (TBIs) affect millions of people each year. Research investigating repeated or serial damage in the form of lesions indicates that behavioral deficits are reduced in animals given sequential lesions separated by a sufficient period of recovery. In the lesion literature, this phenomenon is known as the serial lesion effect (SLE). Although the SLE phenomenon is established in the lesion literature, it has not been thoroughly investigated under current models of brain injury. In the current study, a controlled cortical impact of the bilateral frontal cortex was performed in either a single procedure or a serial procedure separated by two weeks. Rats were tested on the Morris water maze, bilateral tactile adhesive removal task, rotarod and Barnes maze task to determine behavioral deficits. Histology was performed to determine lesion size and astrocyte and microglial response. A serial lesion effect was demonstrated across a majority of the behavioral tasks. However, histological analyses did not suggest a clear mechanistic link to the behavioral phenomena. This is the first study to demonstrate the SLE in a model of TBI, suggesting that behavioral deficits may actually be reduced in repeated head injuries, given an adequate time window between injuries.

Multiple Realizability, Identity Theory, and the Gradual Reorganization Principle

In the literature on multiple realizability and the identity theory, cases of neural plasticity have enjoyed a very limited role. The present article attempts to remedy this small influence by arguing that clinical and experimental evidence of quite extensive neural reorganization offers compelling support for the claim that psychological kinds are multiply realized in neurological kinds, thus undermining the identity theory. In particular, cases are presented where subjects with no measurable psychological deficits also have vast, though gradually received, neurological damage. Common objections and concerns are also discussed and rejected. 1 Introduction 2 The GRP, Serial Lesion Effect, and Multiple Realizability 2.1 A case study of the serial lesion effect 2.2 Evaluating the case study’s evidence for multiple realizability 3 The GRP More Generally 4 Objections to the GRP as Evidence for Multiple Realizability 4.1 Small plastic effects and neurological taxonomies 4.2 But do neural regions and locations even matter at all? 4.3 But are there not other options besides location? 5 Conclusion

Brain recovery – towards an unified theory

Brain recovery – towards an unified theory

Precision and reliability for measurement of change in MRI lesion volume in multiple sclerosis: a comparison of two computer assisted techniques

OBJECTIVEThe serial quantification of MRI lesion load in multiple sclerosis provides an effective tool for monitoring disease progression and this has led to its increasing use as an outcome measure...

Male rat copulation following 6-OHDA lesions of the medial preoptic area: resistance to repeated administration and rapid behavioral recovery

Dopamine (DA) in the medial preoptic and (MPOA) has been shown to facilitate male rat sexual behavior. However, injections of the catecholamine (CA) neurotoxin 6-OHDA into the MPOA did not impair copulation in tests 3 days after injection. In the present study, three weekly (serial) injections produced no copulatory deficits compared to animals that received a single injection or to preinjection copulatory behavior scores. However, blocking CA synthesis, which did not impair control rats, produced deficits in both single and serial lesion animals, with significantly fewer serial than single lesion animals initiating copulation. Biochemical analysis of tissue punches showed no difference in MPOA concentrations of dopamine, norepinephrine, epinephrine, or the dopamine metabolite DOPAC between the two groups. Additional animals were tested at earlier intervals after 6-OHDA injections into the MPOA. Tests conducted 30 min after an MPOA injection 6-OHDA revealed that all measures of copulation were impaired, relative to scores 24 h later. However, these scores were not significantly different from animals tested 30 min after a vehicle injection. A final group, tested 4 h after injection, showed impairment of all measures of copulation compared to vehicle injections and to tests 24 h later. Furthermore, in the tests 24 h later, 6-OHDA animals were not different from vehicle animals. Results from all experiments show that 6-OHDA injections into the MPOA impair copulation for at least 4 h, but that behavioral recovery is complete 24 h later. However, deficits can be reinstated by inhibiting DA synthesis, suggesting that increased synthesis in undamages terminals contributed to behavioral recovery.

"Recovery of sensorimotor function after frontal cortex damage in rats: Evidence that the serial lesion effect is due to serial recovery": Correction.

"Recovery of sensorimotor function after frontal cortex damage in rats: Evidence that the serial lesion effect is due to serial recovery": Correction.

Recovery of sensorimotor function after frontal cortex damage in rats: Evidence that the serial lesion effect is due to serial recovery.

Recovery of sensorimotor function after frontal cortex damage in rats: Evidence that the serial lesion effect is due to serial recovery.

Recovery of sensorimotor function after frontal cortex damage in rats: evidence that the serial lesion effect is due to serial recovery.

Multiple-staged brain lesions produce fewer and smaller behavioral effects than does damage produced in a single surgery. This is called the serial lesion effect. Two hypotheses were tested, the reduced deficit hypothesis and the serial recovery hypothesis, which attempt to explain the serial lesion effect. The effects of lesions of the medial frontal cortex on sensorimotor behavior were investigated in rats that received bilateral damage in a single surgery (n = 7), in two unilateral stages separated by 3 weeks (n = 16), or unilateral damage followed 3 weeks later by a sham surgery (n = 5). Unilateral damage produced deficits on the contralateral side in responsivity to visual, tactile, and olfactory stimuli and impairments in roll-over and paw withdrawal motor responses. All behavioral impairments except visual placement recovered over the next 3 weeks. A second unilateral lesion on the contralateral side produced the same symptoms but on the opposite side of the body. There was no reinstatement of the previously recovered deficits. Bilateral damage incurred in a single stage produced these same deficits on both sides. Because the effects of the second unilateral lesion in the two-stage group produced comparable contralateral effects to those produced in the single-stage group, but no reinstatement of ipsilateral deficits occurred, the reduced deficit hypothesis was rejected. It was concluded that at least for medial frontal cortex damage, the serial lesion effect occurred as a result of serial recovery of the deficits.

Serial lesion effect in rat medial frontal cortex as a function of age

—This experiment examined the potential for behavioral recovery in juvenile, adult, and senescent rats following serial lesions of medial frontal cortex. The subjects were trained on spatial delayed alternation in a T-maze under conditions designed to enhance the probability of a a serial lesion effect. All subjects were given extensive handling and adaptation to the maze, interoperative training, and long interoperative and postoperative intervals. There were several major behavioral findings: (a) the aged intact subjects were not impaired in their ability to learn spatial delayed alternation, (b) one-stage bilateral lesions of frontal cortex produced equivalent deficits on spatial delayed alternation at all ages, (c) subjects in all of the ages, (c) subjects in all of the age categories demonstrated a serial lesion effect, but (d) the 150 day and 570 day serial lesion groups demonstrated significantly better performances than the 35 day serial lesions group on several measures of performance.

Spontaneous mutations in cowpea mosaic virus overcoming resistance due to hypersensitivity in cowpea

Inoculation of the hypersensitlvely reacting cowpea variety “Early Red” with cowpea mosaic virus (CPMV) strain Sb results in brown necrotic local lesions in all plants and in systemic symptoms in some. From mosaic diseased and from necrotic trifoliolate leaves two systemic variant strains were isolated, called S1 and S8, respectively. In Early Red, S1 induced chlorotic local spots and systemic mosaic, S8 caused necrotic local lesions, veinal necrosis and death of the plants. In vitro recombination with strain Sb showed the syndromes of S1 and S8 to be governed by the RNAs of the bottom (B)-components. To establish whether the systemic variants were spontaneous mutants or pre-existing contaminants, Early Red plants were inoculated with nitrous acid-induced mutants of Sb, carrying symptom markers on other hosts in their B-RNAs. Again mosaic- and necrosis-inducing strains could be isolated, this time carrying the symptom markers of the mutant parent strains. In serial local lesion transfers these new variants were phenotypically stable and homogeneous. Supplementation tests with separated components of Sb confirmed that the transition from localized to systemic infection was due to changes in their B-components. These results demonstrated that strains with increased virulence in Early Red can be generated by spontaneous mutation. Analysis of F1- and F2,-generations of crosses between Early Red and the sensitive variety “Blackeye Early Ramshorn” showed that the differential local and systemic reactions of the two varieties to Sb-infection are governed by 1 gene. The Early Red-allele, specifying necrotic local reaction, is dominant over the allele in Blackeye Early Ramshorn, determining chlorotic local reaction. With respect to systemic infection the dominance relationship is reversed, susceptibility to systemic spread, as shown by Blackeye Early Ramshom, being dominant over localization of infection, which is normally found in Early Red. As the breakdown of resistance due to hypersensitivity of Early Red was also observed with newly obtained field isolates of CPMV this type of resistance seems to have limited value for protection of cowpea against CPMV.

Effects of one- and two-stage lesions of the posterior hypothalamus on temperature regulation in the rat

Rats received 1-stage bilateral or sequential unilateral (serial) lesions of the posterior hypothalamus and were tested for the ability to regulate body temperature after a lengthy recovery period. The groups with lesion differed from the sham-operated groups in the cold, although not under ambient or warm conditions. The fact that the serial lesion group performed the same as the 1-stage lesion groups in the cold is significant because earlier tests on these same animals revealed much better recovery after serial lesions in swimming, and a partial serial lesion effect in open field performance.

Limited sparing of function on spatial delayed alternation after two-stage lesions of prefrontal cortex in the rat

Adult rats with complete removals of medial prefrontal cortex (MF) either in 1-stage or 2-stages were tested on a spatial delayed alternation task with a 50 day interoperative interval and with specific training during the interoperative interval. There were two groups receiving 2-stage lesions: one group received a complete lesion of MF cortex in one hemisphere at first surgery followed by a comparable lesion in the other hemisphere at second surgery; the second group received a bilateral lesion of the dorsal component of MF cortex at first surgery followed by bilateral removal of the remaining ventral component at second surgery. The animals in both serial lesion groups were imparied relative to sham operated controls, but they were significantly less impaired than animals receiving similar lesions in a single stage. Several conclusions are drawn from these results: (1) significant sparing of function can be demonstrated after complete serial destruction of MF cortex, but the sparing is not complete. (2) the provision of interoperative experience and a prolonged interoperative interval enhances the degree of sparing observed with 2-stage MF removals as it does with serial lesions of other brain areas. (3) equivalent sparing of function was observed with both serial lesion techniques. Thus, it is not necessary that one hemisphere remain undamaged during the interoperative interval; nor is it necessary that any portion of MF cortex be spared bilaterally during the interoperative interval.

Disruption and recovery of locomotor and manipulatory behavior following cortical lesions in rats

The first experiment demonstrated that removals of frontal cortex disrupted manipulation (latch opening) but not locomotion; damage of medial parietal cortex (sensorimotor cortex) produced the reverse effects. In the second study, serial lesions of medial parietal cortex resulted in more rapid recovery of locomotion than damage imposed in a single operation. Cinematographic analysis of locomotor movements indicated differences in the hindlimb patterns between animals with medial parietal lesions that had recovered and sham-operated controls. In contrast to these findings, a third experiment produced no evidence of serial lesion effects following one- and two-stage frontal damage.

Effects of successive bilateral hippocampectomy on DRL 20 performance in rats

The effects of single-stage versus two-stage, successive bilateral hippocampectomy on acquisition of a DRL 20 operant schedule were determined. Rats received training on a continuous reinforcement operant schedule prior to either single-stage total hippocampectomy, sham operative treatment or bilateral lesion of either dorsolateral or posteroventral hippocampus. After forty days of DRL 20 training, the seriatim groups received bilateral lesions of remaining hippocampal tissue. All animals then received fifteen final days of DRL 20 training. The single-stage lesion group was found, for all sessions, to be significantly less efficient than the sham operates. During interoperative training the two seriatim groups were equally efficient and did not differ from the sham operates. However, after the second serial lesion, the group that had received an initial lesion of the posteroventral hippocampus decreased DRL performance to a level equal to that of the single-stage group while the group which had initially received anterodorsal lesions maintained efficient DRL performance.

Progressive brain damage accelerates axon sprouting in the adult rat.

An entorhinal cortical lesion causes undamaged fibers in the deafferented hippocampus to sprout and form new connections within 4 to 7 days after the lesion was made. When a partial lesion of the entorhinal cortex precedes a second, more complete entorhinal lesion by a few days, the rate of axon sprouting is accelerated so that the response to the second lesion occurs within only 2 days. This priming effect is present within 4 days, lasts for a few weeks, and eventually subsides. This acceleration may explain, in part, the faster recovery and reduced deficits seen in behavioral studies that have followed serial lesion paradigms.

The differential effects of additional cortical lesions in rats with single- or multiple-stage lesions of the visual cortex

Male albino rats relearned a black-white discrimination for food after posterior neocortex was bilaterally removed in a single operation (“single stage”) or in two unilateral operations (“multiple stage”). Single-stage animals showed no savings in relearning (relearning errors = learning errors). Multiple-stage animals showed positive savings (relearning errors < learning errors). To assess cortical reorganization, the rats were given additional lesions and again retrained. Cortex either contiguous or noncontiguous with the posterior lesion was removed bilaterally. Contiguous and noncontiguous lesions produced different effects only among animals with prior multiple-stage posterior lesions. Rats with single-stage posterior lesions and contiguous or noncontiguous lesions showed positive savings and did not differ from each other or from rats with multiple-stage posterior and noncontiguous lesions. Rats with multiple-stage posterior and contiguous lesions made more errors and showed negative savings. The role of contiguous cortex in the serial lesion effect was also tested with two additional groups. Rats given noncontiguous cortex lesions prior to multiple-stage posterior lesions showed positive savings in retraining. Rats given contiguous cortex lesions prior to multiple-stage posterior lesions showed negative savings.

Age and serial ablations of somatosensory cortex in the rat

The present study investigated the effects of one-stage and two-stage ablations of somatosensory cortex at 30 days, 270 days and 570 days of age on the acquisition of tactile discriminations in rats. Deficits in the ability to acquire tactile discriminations following such cortical lesions appeared to be similar regardless of the age at which the damage was sustained. Serial placement of the lesions did not attenuate the deficits in 30-day or 570-day-old rats. Some mitigation of the impairment was present in animals sustaining serial surgery at 270 days of age. In contrast, rats sustaining one-stage lesions at 570 days of age performed somewhat better than their age-mates sustaining two-stage lesions. Factors possibly relevant to the serial lesion effect and to recovery of function in general are suggested.

Effects of serial lesions of somatosensory cortex and further neodecortication on retention of a rough-smooth discrimination in rats.

Five groups of rats with bilateral lesions of the somatosensory cortex and one of animals sustained only sham operations were tested for retention of a rough-smooth discrimination. Two of the lesion groups had sequential unilateral ablations, in one case with interoperative testing, and three groups had one-stage bilateral lesions. The two groups of animals with serial lesions did not differ from each other or from sham operates in relearning the task. RAts with one-stage lesions and preoperative overtraining also performed well, but the other one-stage groups showed deficits relative to control and serial lesion groups. In the second experiment the sham operated rats from Experiment 1 experiences lesions anterior and posterior to the somatosensory zones. These lesions did not affect retention. Somatosensory cortex then was ablated in one operation and severe performance decrements were seen. Removal of additional neocortex in a sample of animals that had relearned the discrimination after one-stage somatosensory cortex lesions (Exp. 1) also affected retention. In contrast, retention was not impaired on some of the measures in those animals that originally had two-stage ablations. The findings from these two experiments show that some ablation effects can be circumvented with overtraining or serial lesion techniques. The data also indicate that non-somatosensory cortex may play a role in recovery after somatic cortex lesions, but that the substrates underlying recovery might not be the same after one-stage and two-stage ablations.