Meniscus Allograft Transplantation in Conjunction with Arthroscopic Biologic Knee Restoration Delays Arthroplasty in Patients Over 50 Years of Age.

PURPOSE: The purpose of this study is to evaluate the utility of meniscus allografts in combination with other procedures to delay knee arthroplasty in patients older than 50 years of age previously advised joint arthroplasty. METHODS: One hundred eight meniscus allograft transplants (MATs) using the arthroscopic three tunnel technique between 1997 and 2019 in patients over 50 years of age were retrospectively reviewed with two-year minimum follow-up period. Inclusion criteria were patients recommended knee arthroplasty with pain and preservation of some joint space by standing flexion x-rays. Exclusion criteria were lack of joint space, failure to comply with rehabilitation protocol or complete research questionnaires. International Knee Documentation Committee (IKDC) composite and isolated pain scale were evaluated longitudinally. Time from MAT to arthroplasty was measured with failure defined as allograft excision or revision, progression to arthroplasty, or same or increased pain. RESULTS: Eighty-six of 108 (79.6%) patients met eligibility criteria. Over the follow-up mean 8.55 (range of 0.68 to 25.2) years, 42 of 87 (48.2%) grafts progressed to arthroplasty with mean time of 8.64 (median 8.05) years. Concomitant procedures did not have significant impact on survival; however, survival medians were higher among paste graft and chondroplasty and lower among osteotomy groups. At the time of reporting, 41 of 84 (48.8%) patients had intact meniscus transplants, demonstrating significant improvements (p<0.001) in pain and function as assessed by IKDC. These improvements were sustained ten years post-operatively, correlated to a mean of 65.8 years of age. At least 50% of patients achieved Minimal Clinically Important Difference (MCID) through 10 years post-operatively. CONCLUSIONS: Meniscus allografts in combination with other arthroscopic interventions delay knee arthroplasty and improve knee symptoms of pain and function in a population of knee arthroplasty candidates over 50 years of age. Influences of concomitant procedures cannot be defined.

Adult neurogenesis occurs in primate sensorimotor cortex following cervical dorsal rhizotomy.

Adult neurogenesis remains controversial in the cerebral cortex. We have previously shown in monkeys and rats that reactive neurogenesis occurs in the spinal dorsal horn 6-8 weeks after a cervical dorsal rhizotomy. Here, in three monkeys with the same lesion, we asked whether it also occurs coincidentally in the corresponding primary somatosensory and motor cortex, where significant topographic and neuronal reorganization is known to occur. Monkeys (male Macaca fascicularis) were given 5-bromo-2-deoxyuridine (BrdU) injections 2-3 weeks after the rhizotomy, and were perfused 4-6 weeks later. Cells colabeled for BrdU and five different neuronal markers were observed within the primary somatosensory and motor cortex, and their distributions were compared bilaterally. Cells colabeled with BrdU and the astrocytic marker glial fibrillary acidic protein (GFAP) were also quantified for comparison. A significant number of BrdU/NeuN- and BrdU/calbindin-colabeled cells were observed in topographically reorganized cortex. Small numbers of BrdU/GFAP-colabeled cells were also consistently observed bilaterally, but these cells were never colabeled with any of the neuronal markers. Of the cells colabeled with BrdU and a neuronal marker, at least half had an inhibitory phenotype. However, excitatory pyramidal neurons were also identified with classic pyramidal morphology. Cortical neurogenesis was not observed in other cortical regions. It was also not observed in the primary sensorimotor, prefrontal, or posterior parietal cortex in an additional control monkey (male Macaca fascicularis) that had no surgical intervention. Our findings provide evidence for reactive endogenous cortical neurogenesis after a dorsal rhizotomy, which may play a role in functional recovery.

Might astrocytes play a role in maintaining the seizure-prone state?

The amygdala-kindling model is used to study complex partial epilepsy with secondary generalization. The present study was designed to (A) quantify astrocytic changes in the piriform cortex of amygdala-kindled subjects over time and (B) investigate the role that astrocytes might play in maintaining the seizure-prone state. In Study A, once the experimental subjects reached five stage 5 seizures, stimulation was stopped, and both kindled and control rats were allowed to survive for the interval appropriate to their group (7, 18, 30, or 90 days). Following each interval, the kindled and control animals were given 10 intraperitoneal injections of bromodeoxyuridine (BrdU) and sacrificed 24 h following the last injection. Significantly higher numbers of dividing astrocytes (identified by co-labeling for BrdU and to one of the astrocytic intermediate filament proteins glial fibrillary acidic protein or vimentin) were found in the kindled brains. All kindled groups had significantly higher numbers of double-labeled cells on the side contralateral to the stimulation site, except for those in the 90 day survival group. In Study B, rats were implanted with chemotrodes, were kindled as in Study A, and were subsequently infused with either saline or with L alpha-AA (to lesion astrocytes) during a further 25 stimulations (1/day). L alpha-AA infused rats had significantly diminished levels of behavioral seizures, higher after discharge thresholds, lower after discharge durations, and decreased numbers of double-labeled astrocytes in piriform cortex than did saline infused rats. Together, the data indicate that astrocytes may play a role in maintaining the seizure-prone state.

Astrocytic proliferation in the piriform cortex of amygdala-kindled subjects: a quantitative study in partial versus fully kindled brains.

Complex partial epilepsy is a seizure disorder in which attacks frequently arise from foci located in the temporal lobes. The amygdala-kindling model is a widely used model of complex partial epilepsy with secondary generalization. The present study was designed to quantitatively assess astrocytic changes in the rat piriform cortex in the amygdala-kindling model of epilepsy. Bromodeoxyuridine-injected subjects were sacrificed 24 h after the first stage 1 or fifth stage 5 seizure. Brain sections were prepared and examined quantitatively. A significantly higher number of dividing astrocytes (identified by co-labeling with antibodies to bromodeoxyuridine and to one of the astrocytic intermediate filament proteins glial fibrillary acidic protein or vimentin) was found in both partially kindled (stage 1) and fully kindled (stage 5) brains. The partially kindled brains had a significantly higher number of double-labeled cells on the side ipsilateral to stimulation. The opposite trend was observed in the fully kindled brains. Differences between the ipsilateral and contralateral sides of the kindled brain may suggest different role(s) for astrocytes in the development and progression of the seizure-prone state.

Adult neurogenesis in primate and rodent spinal cord: comparing a cervical dorsal rhizotomy with a dorsal column transection.

Neurogenesis has not been shown in the primate spinal cord and the conditions for its induction following spinal injury are not known. In the first part of this study, we report neurogenesis in the cervical spinal dorsal horn in adult monkeys 6-8 weeks after receiving a well-defined cervical dorsal rhizotomy (DRL). 5-bromo-2-deoxyuridine (BrdU) was administered 2-4 weeks following the lesion. Cells colabeled with BrdU and five different neuronal markers were observed in the peri-lesion dorsal horn 4-5 weeks after BrdU injection. Those colabeled with BrdU and neuron-specific nuclear protein, and BrdU and glial fibrillary acidic protein were quantified in the dorsal horn peri-lesion region, and the ipsi- and contralateral sides were compared. A significantly greater number of BrdU/neuron-specific nuclear protein- and BrdU/glial fibrillary acidic protein-colabeled cells were found on the lesion side (P<0.01). These findings led us to hypothesize that neurogenesis can occur within the spinal cord following injury, when the injury does not involve direct trauma to the cord and glial scar formation. This was tested in rats. Neurogenesis and astrocytic proliferation were compared between animals receiving a DRL and those receiving a dorsal column lesion. In DRL rats, neurogenesis was observed in the peri-lesion dorsal horn. In dorsal column lesion rats, no neurogenesis was observed but astrocytic activation was intense. The rat data support our hypothesis and findings in the monkey, and show that the response is not primate specific. The possibility that new neurons contribute to recovery following DRL now needs further investigation.