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Jacques Penderis

Publications and source records attributed to Jacques Penderis.

9 recordsLinked to original sources

Females remyelinate more efficiently than males following demyelination in the aged but not young adult CNS.

To assess the effects of sex on CNS remyelination, demyelinating lesions were induced by injection of ethidium bromide into the caudal cerebellar peduncle of Sprague-Dawley rats divided into the following 8 groups: young adult male, young adult female, old adult male and old adult female and each of these in which the gonads had been removed 4 weeks prior to lesion induction. Remyelination was assessed, blinded to grouping, by a ranking analysis using standard morphological criteria. In young adult animals, where remyelination proceeds rapidly, there was no difference in the remyelination at four weeks after lesion induction in male or females regardless of whether they were intact or castrated/ovariectomised. However, in old adult rats, where remyelination proceeds slowly, the extent of oligodendrocyte remyelination was significantly less in males compared to females at 8 weeks after lesion induction. Removal of gonads did not affect remyelination in old rats of either gender. These results indicate a sex-associated divergence in remyelination efficiency that occurs with ageing that is unaffected by the removal of gonadal sources of sex steroid hormones.

Aging↗

Effects of pre- versus post-anaesthetic buprenorphine on propofol-anaesthetized rats.

OBJECTIVE: To compare the effect of pre- versus post-anaesthetic intramuscular (IM) buprenorphine on intermittent intravenous (IV) propofol anaesthesia in rats. ANIMALS: Twenty healthy, adult, female, ex-breeder Sprague-Dawley rats within the mass range 274-379 g. MATERIALS AND METHODS: Animals were randomly allocated to one of two groups. Group 1 (n = 10) received 9 mug buprenorphine (IM) at the start and group 2 (n = 10) received the same dose buprenorphine at the end of anaesthesia. Five animals from each group (randomly selected) received a standardized 40-minute surgical procedure (procedure 1), the remaining half, a standardized 60-minute surgical procedure (procedure 2). Induction of anaesthesia with 4% isoflurane carried in oxygen was immediately followed by IV propofol (3 mg) and intraperitoneal diazepam (500 microg). Anaesthesia was maintained using periodic IV propofol (500 microg) injected through an indwelling tail vein cannula, by an operator ignorant of the buprenorphine status. One hour after recovery from anaesthesia, the animals' level of awareness were scored by an observer ignorant of both the buprenorphine status and the total propofol dose administered. RESULTS: Buprenorphine administration at the start of anaesthesia versus administration at the end resulted in a significant reduction in the total per-kilogram requirement for propofol from a mean of 24 mg kg(-1) (+/-2.5 mg kg(-1), n = 5) to 5.5 mg kg(-1) (+/-1.1 mg kg(-1), n = 5) for procedure 1, and from a mean of 30 mg kg(-1) (+/-1.2 mg(-1), n = 5) to 16 mg kg(-1) (+/-1.0 mg kg(-1), n = 5) in procedure 2. Animals receiving buprenorphine at the start of anaesthesia demonstrated a higher level of awareness 1 hour after cessation of anaesthesia. No adverse effects were evident in either group 24 hours after recovery. CONCLUSIONS: Buprenorphine administration at the start of periodic IV propofol anaesthesia in rats resulted in a significant reduction in the total propofol requirement and significantly improved the 1-hour post-anaesthesia recovery score. Clinical relevance Besides the ethical advantage of pre-emptive analgesia, pre-anaesthetic medication with buprenorphine in rats significantly reduces the total propofol requirements for surgical anaesthesia and in this study was found to be a safe and effective method of anaesthesia.

Analgesics, Opioid↗

Increasing local levels of neuregulin (glial growth factor-2) by direct infusion into areas of demyelination does not alter remyelination in the rat CNS.

Glial growth factor-2 (GGF-2) is a neuronally derived isoform of neuregulin shown in vitro to promote proliferation and survival of oligodendrocytes, the myelinating cells of the CNS. Enhanced remyelination has been demonstrated in vivo following systemic delivery of human recombinant GGF-2 (rhGGF-2) in experimental autoimmune encephalomyelitis (EAE). However, it is uncertain whether this is the result of direct effects of rhGGF-2 on cells of the oligodendrocyte lineage or due to modulation of the immune or inflammatory response. If this enhanced remyelination was due to direct effects of rhGGF-2 on cells of the oligodendrocyte lineage then one would expect rhGGF-2 to induce a similar proremyelinating response in nonimmune, gliotoxin models of demyelination. Using a gliotoxin model of demyelination we were therefore able to ascertain the in vivo effect of rhGGF-2 following local CNS delivery in a model that is not confounded by the concurrent presence of an immune-mediated process. No significant alteration in the rate or character of remyelination was evident following local delivery as compared to controls, and indeed nor following systemic delivery in the gliotoxin model. The results of this study therefore indicate that both direct infusion and systemic delivery of rhGGF-2 do not alter remyelination in a nonimmune, gliotoxin model of demyelination. This suggests that the proremyelinating effects of systemically delivered rhGGF-2 in EAE are unlikely to be due to direct effects on the oligodendrocyte lineage, but may be mediated by rhGGF-2 inducing an environment more favourable to remyelination, possibly through modulation of the immune response.

Animals↗

Impaired remyelination and depletion of oligodendrocyte progenitors does not occur following repeated episodes of focal demyelination in the rat central nervous system.

It has been hypothesized that the progressive failure of remyelination in chronic multiple sclerosis is, in part, the consequence of repeated episodes of demyelination at the same site, eventually depleting oligodendrocyte progenitor cells (OPCs) and exhausting the remyelinating capacity. We investigated the effect of previous focal, ethidium bromide-induced demyelination of brain stem white matter (with intervening recovery) on the efficiency of the remyelination process during second and third subsequent episodes of demyelination, and the OPC response during a second episode of demyelination. Previous focal demyelinating lesions followed by recovery did not result in any retardation of the remyelination process, nor did they alter the proportion of Schwann cell versus oligodendrocyte remyelination. The OPC response during remyelination was quantified by in situ hybridization using a probe to platelet-derived growth factor-alpha receptor (PDGF alpha R), an OPC-expressed mRNA. Following recovery from focal, toxin-induced CNS demyelination, the OPC density returned to levels equivalent to those in normal white matter. Further more, there was no depletion of OPCs following repeated episodes of focal, toxin-induced CNS demyelination at the same site. These results indicate that repeated CNS demyelination, which has the opportunity to repair in the intervening period, is not characterized by impaired remyelination or depletion of OPCs.

Animals↗

The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation.

The age-associated decrease in the efficiency of CNS remyelination has clear implications for recovery from demyelinating diseases such as multiple sclerosis (MS) that may last for several decades. Developing strategies to reverse the age-associated decline requires the identification of how the regenerative process is impaired. We addressed whether remyelination becomes slower because of an impairment of recruitment of oligodendrocyte progenitors (OPs) or, as is the case in some MS lesions, an impairment of OP differentiation into remyelinating oligodendrocytes. The OP response during remyelination of focal, toxin-induced CNS demyelination in young and old rats was compared by in situ hybridization using probes to two OP-expressed mRNA species: platelet-derived growth factor-alpha receptor and the OP transcription factor myelin transcription factor 1 (MyT1). We found that the expression patterns for the two OP markers are very similar and reveal a delay in the colonization of the demyelinated focus with OPs in the old animals compared with the young animals. By comparing the mRNA expression pattern of MyT1 with that of the myelin proteins myelin basic protein and Gtx, we found that in the old animals there is also a delay in OP differentiation that increases with longer survival times. These results indicate that the age-associated decrease in remyelination efficiency occurs because of an impairment of OP recruitment and the subsequent differentiation of the OPs into remyelinating oligodendrocytes, and that strategies aimed at ameliorating the age-associated decline in remyelination efficiency will therefore need to promote both components of the regenerative process.

Age Factors↗

Intraventricular tension pneumocephalus as a complication of transfrontal craniectomy: a case report.

OBJECTIVE: To report the diagnosis and surgical treatment of a case of intraventricular tension pneumocephalus in a dog after a transfrontal craniectomy for removal of a falx cerebri meningioma. STUDY DESIGN: Case report. ANIMAL: A 12-year-old spayed English springer spaniel. RESULTS: Intraventricular air and a fistula between the craniectomy site and ventricular system were identified by magnetic resonance imaging. Prompt repair of the dural defect using prosthetic dura mater resulted in immediate regression of the neurological signs and cerebral spinal fluid rhinorrhea. Magnetic resonance imaging repeated 8 weeks after surgery showed complete resolution of pneumocephalus. CONCLUSIONS AND CLINICAL RELEVANCE: Tension pneumocephalus is an uncommon but life-threatening complication of craniectomy that requires urgent diagnosis and treatment.

Animals↗

Use of traction during magnetic resonance imaging of caudal cervical spondylomyelopathy ("wobbler syndrome") in the dog.

Cervical spondylomyelopathy or "wobbler syndrome" is a well-defined disorder of large-breed dogs, characterized by a compressive lesion affecting the cervical spinal cord that in many dogs may have a dynamic component. Determination of whether this dynamic component is present is important in the decision-making process as regards therapeutic intervention. Despite a significant risk of neurologic deterioration following myelography in some large dogs affected by wobbler syndrome, myelography is considered an essential part of the assessment, primarily as it allows assessment of whether a dynamic compression exists. This same neurologic deterioration is not apparent following magnetic resonance (MR) imaging; however, the use of MR imaging in the investigation of wobbler syndrome has thus far been limited by the inability to perform the traction studies required to ascertain whether a dynamic component to the spinal cord compression exists. This paper presents a technique of applying traction during MR imaging of the cervical spine to reduce a dynamic wobbler syndrome lesion.

Animals↗