Kamila Saganová

A Simple and Reproducible Model of Spinal Cord Injury Induced by Epidural Balloon Inflation in the Rat

This paper describes a modification of a balloon-compression technique to produce spinal cord injury in adult rats. A 2-French Fogarty catheter is inserted into the dorsal epidural space through a small hole made in T10 vertebral arch, advanced cranially to T8-9 spinal level, and inflated for 5 min. Spinal cord damage is graded by increasing the volume of saline used to inflate the balloon. Quantitative neurological and histopathological outcomes are presented with three different volumes (10, 15, and 20 microl of saline) to characterize the gradation of injury. Volume of 15 microl produced complete paraplegia followed by gradual recovery, finally reaching approximately the middle of the scale used to quantitate the locomotor performance. With these animals, after 4 weeks, the center of the lesion shows complete loss of grey matter and partial sparing of the white matter. We conclude that 15 microl volume produced submaximal injury that will be useful for studying the pathophysiology and effects of protective therapies with this compression-injury model.

Limited minocycline neuroprotection after balloon-compression spinal cord injury in the rat

Minocycline (MC), a second-generation tetracycline and anti-inflammatory agent reportedly provides neuroprotection following CNS injury. The objective of this study was to examine the neuroprotective effects of short and long-term MC treatment using balloon-compression spinal cord injury (SCI) in the rat. Rats subjected to SCI were treated with MC for 1 day (1DMC group; total dose 180 mg/kg) or 5 days (5DMC group; total dose 450 mg/kg) or placebo. The effects of MC treatment on locomotor recovery (BBB scale) and spinal cord white and gray matter sparing were evaluated for up to 28 days. Morphometric analysis showed that while MC treatment spared spinal cord white and gray matter rostral to the lesion epicenter in both, 1DMC and 5DMC groups, sparing of white and gray matter areas was not observed caudal to the traumatic lesion. In addition, MC treatment had no effect on final locomotor recovery. Limited improvement of spinal cord post-compression consequences raises questions about the neuroprotection efficiency of MC treatment following compression SCI in the rat.

Immunosuppressant FK506: focusing on neuroprotective effects following brain and spinal cord injury.

The secondary damage that follows central nervous system (CNS) injury is a target for neuroprotective agents aimed at tissue and function sparing. FK506, a clinically used immunosuppressant, acts neuroprotectively in rat models of brain and spinal cord injury and ischemia. Evidence of in vivo experimental studies highlights the neuroprotective role of FK506 by its direct impact on various cell populations within the CNS. The participation of FK506 in modulation of post-traumatic inflammatory processes is a further potential aspect involved in CNS neuroprotection. In this review we provide an overview of the current laboratory research focusing on the multiple effects of FK506 on neuroprotection following CNS injury.

Intrathecal administration of dizocilpine maleate (MK-801) attenuates ischemic damage in the rabbit spinal cord

The therapeutic efficacy of intrathecally administered MK-801 (dizocilpine maleate), a noncompetitive receptor antagonist of N-methyl-D-aspartate receptor complex, was investigated in a rabbit spinal cord ischemia model. Normal saline, 0.3 ml (control, n = 4) or MK-801, 150 micrograms in 0.3 ml of saline, was administered intrathecally at the level of the lumbar enlargement, 30 min before (pretreatment, n = 7) or in the first min after (post-treatment, n = 4) 30 min of aortic occlusion followed by 2-h reperfusion. Nauta silver method was used for histopathological evaluation of lumbosacral segments. The degree of gray matter damage (argyrophilic neurons) was evaluated in three areas: A1, Rexeds laminae I-VI; A2, laminae VII and X; and A3, laminae VIII-IX. Pre- and post-treatment with MK-801 decreased the number of argyrophilic neurons (P < 0.05) in all areas examined. The number of argyrophilic neurons in A1, A2, and A3 was reduced by 59, 28, and 29%, respectively, by MK-801 pretreatment and by 87, 66, and 46%, respectively, by MK-801 post-treatment. Our results show that with single bolus intrathecal administration the efficacy of MK-801 was greater with post- compared to pretreatment and most dramatic in Rexeds laminae I-VI compared to laminae VII-X. Intrathecal administration of MK-801 prior to or at the beginning of the recirculation diminishes the extent of postischemic neuronal spinal cord damage at early postreperfusion period.

Effects of short-duration electromagnetic radiation on early postnatal neurogenesis in rats: Fos and NADPH-d histochemical studies.

The immediate effects of whole body electromagnetic radiation (EMR) were used to study postnatal neurogenesis in the subventricular zone (SVZ) and rostral migratory stream (RMS) of Wistar rats of both sexes. Newborn postnatal day 7 (P7) and young adult rats (P28) were exposed to pulsed electromagnetic fields (EMF) at a frequency of 2.45 GHz and mean power density of 2.8 mW/cm(2) for 2 h. Post-irradiation changes were studied using immunohistochemical localization of Fos and NADPH-d. We found that short-duration exposure induces increased Fos immunoreactivity selectively in cells of the SVZ of P7 and P28 rats. There were no Fos positive cells visible within the RMS of irradiated rats. These findings indicate that some differences exist in prerequisites of proliferating cells between the SVZ and RMS regardless of the age of the rats. Short-duration exposure also caused praecox maturation of NADPH-d positive cells within the RMS of P7 rats. The NADPH-d positive cells appeared several days earlier than in age-matched controls, and their number and morphology showed characteristics of adult rats. On the other hand, in the young adult P28 rats, EMR induced morphological signs typical of early postnatal age. These findings indicate that EMR causes age-related changes in the production of nitric oxide (NO), which may lead to different courses of the proliferation cascade in newborn and young adult neurogenesis.

Regional differences of proliferation activity in the spinal cord ependyma of adult rats

Increased proliferation activity in the central canal ependyma of adult rodent spinal cord was described after injury and is thought to participate in recovery processes. Proliferation activity is scarce under physiological conditions, but still could be of importance, as in vitro studies showed that the spinal cord ependyma is an internal source of neural stem cells. Data from these studies indicate that there are regional differences in the distribution of proliferation activity along the rostro-caudal axis. We analyzed the proliferation activities in the ependyma within the entire extent of intact adult rat spinal cord. To identify proliferating cells we performed immunohistochemistry either for cell cycle S-phase marker BrdU or for the nuclear protein Ki-67. BrdU and Ki-67 positive cells were counted on sections selected from four spinal cord regions — cervical, thoracic, lumbar and sacral/coccygeal. Analysis showed that the number of BrdU positive cells within the ependyma was very low in all subdivisions of the spinal cord. Both BrdU and Ki-67 labeling revealed a significantly higher number of proliferating cells in the ependyma of sacrococcygeal part in comparison to all other spinal cord regions, suggesting that the caudal spinal cord might have potentially higher regeneration capacity compared to more rostral parts.