Ultrastructural Changes of Oligodendroglia and Myelin Sheaths Induced by Ethidium Bromide

Arch. Endocrinol. Metab.

Martins

Bernardi

2015

Objective: The diabetic state induced by streptozotocin injection is known to impair oligodendroglial remyelination in the rat brainstem following intracisternal injection with the gliotoxic agent ethidium bromide (EB). In such experimental model, propentofylline (PPF) recently showed to improve myelin repair, probably due to its neuroprotective, antiinflammatory and antioxidant effects. The aim of this study was to evaluate the effect of PPF administration in diabetic rats submitted to the EB-demyelinating model. Materials and methods: Adult male rats, diabetic or not, received a single injection of 10 microlitres of 0.1% EB solution into the cisterna pontis. For induction of diabetes mellitus the streptozotocin-diabetogenic model was used (50 mg/kg, intraperitoneal route -IP). Some diabetic rats were treated with PPF (12.5 mg/kg/day, IP route) during the experimental period. The animals were anesthetized and perfused from 7 to 31 days after EB injection and brainstem sections were collected for analysis of the lesions by light and transmission electron microscopy. Results: Diabetic rats injected with EB showed larger amounts of myelin-derived membranes in the central areas of the lesions and considerable delay in the remyelinating process played by surviving oligodendrocytes and invading Schwann cells after the 15 th day. On the other hand, diabetic rats that received PPF presented lesions similar to those of non-diabetic animals, with rapid remyelination at the edges of the lesion site and fast clearance of myelin debris from the central area. Conclusion: The administration of PPF apparently reversed the impairment in remyelination induced by the diabetic state. Arch Endocrinol Metab. 2015;59(1):47-53

Section: General Aspects From Eb-induced Lesionssupporting

confidence: 59%

mentioning

confidence: 99%

Propentofylline reverses delayed remyelination in streptozotocin-induced diabetic rats

Arch. Endocrinol. Metab.

Martins

Bernardi

2015

“…With the semi-quantitative analysis (by comparing the domains of the mean scores for groups I and III and their limits -±2SEM -at 31 days), it was evident that CsA treatment in the present study caused an increased oligodendroglial remyelination 14,15 . It is known that CsA permeates into target cells and binds to cyclophilins, a family of peptidyl-prolyl isomerases.…”

Section: Discussionmentioning

confidence: 98%

“…Three semithin sections from each animal at 31 days after EB injection from groups I and III were examined for the presence of axons remyelinated by oligodendrocytes and Schwann cells, as well as for demyelinated axons. Remyelination by either Schwann cells or oligodendrocytes was identified using morphological criteria previously described [2][3][4]6,14,15 . The proportion of each was estimated in a scale ranging from 0 to 5.…”

Section: Methodsmentioning

confidence: 99%

Semi-quantitative analysis of the effects of cyclosporine on remyelination following gliotoxic injection in the brainstem

Martins

Branco

et al. 2011

Arq. Neuro-Psiquiatr.

The use of cyclosporine (CsA) has shown to induce an increase in the density of oligodendrocytes near remyelinating areas following the injection of ethidium bromide (EB), a demyelinating agent, in the rat brainstem. This study was designed in order to evaluate if CsA has the capacity of increasing remyelination. In this context, a comparison between the final balance of myelin repair in CsA treated and non-treated rats was assessed using a semi-quantitative method developed for documenting the extent and nature of remyelination in gliotoxic lesions. Wistar rats were submitted to intracisternal injection of 10 microliters of 0.1% EB. Some were treated during 31 days with CsA (group III -10 mg/kg/day by 7 days and, thereafter, 3 times a week, with a minimal interval of 48 hours) by intraperitonial route. Others were not treated with CsA (group I). A control group was planned receiving into the cisterna pontis 10 microliters of 0.9% saline solution and following after that the same CsA administration protocol (group II). Results clearly demonstrate that in vivo administration of CsA after EB-demyelinating lesions stimulated oligodendrocyte remyelination (mean remyelination scores of 3.72±0.25 for oligodendrocytes and 1.04±0.39 for Schwann cells) compared to non-treated animals (3.13±0.71 and 1.31±0.62, respectively), although the mechanisms by which this positive CsA effect occurs are unclear.

“…The mechanism of disturbance may be related to the fact that Schwann cells are a primary target of polyol pathway abnormalities strongly linked to the hyperglycemia found in diabetes mellitus (3). Schwann cell invasion and contribution to myelin repair in the central nervous system (CNS) are usually seen in the ethidium bromide (EB) demyelinating model (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), where there is early astrocyte disappearance, with both glia limitans and bloodbrain barrier disruption. Oligodendroglial damage induced by EB produces primary demyelinating lesions at the site of injection, with subsequent remyelination performed by surviving oligodendrocytes and by invasive Schwann cells (4)(5)(6)9,(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Delayed Schwann cell and oligodendrocyte remyelination after ethidium bromide injection in the brainstem of Wistar rats submitted to streptozotocin diabetogenic treatment

Lallo

Trigueiro

et al. 2006

Braz J Med Biol Res

Schwann cell disturbance followed by segmental demyelination in the peripheral nervous system occurs in diabetic patients. Since Schwann cell and oligodendrocyte remyelination in the central nervous system is a well-known event in the ethidium bromide (EB) demyelinating model, the aim of this investigation was to determine the behavior of both cell types after local EB injection into the brainstem of streptozotocin diabetic rats. Adult male Wistar rats received a single intravenous injection of streptozotocin (50 mg/kg) and were submitted 10 days later to a single injection of 10 µL 0.1% (w/v) EB or 0.9% saline solution into the cisterna pontis. Ten microliters of 0.1% EB was also injected into non-diabetic rats. The animals were anesthetized and perfused through the heart 7 to 31 days after EB or saline injection and brainstem sections were collected and processed for light and transmission electron microscopy. The final balance of myelin repair in diabetic and non-diabetic rats at 31 days was compared using a semiquantitative method. Diabetic rats presented delayed macrophage activity and lesser remyelination compared to non-diabetic rats. Although oligodendrocytes were the major remyelinating cells in the brainstem, Schwann cells invaded EB-induced lesions, first appearing at 11 days in non-diabetic rats and by 15 days in diabetic rats. Results indicate that short-term streptozotocin-induced diabetes hindered both oligodendrocyte and Schwann cell remyelination (mean remyelination scores of 2.57 ± 0.77 for oligodendrocytes and 0.67 ± 0.5 for Schwann cells) compared to non-diabetic rats (3.27 ± 0.85 and 1.38 ± 0.81, respectively).