Restorative Neurology and Neuroscience - Volume 29, issue 1

Authors: Moralí, Gabriela | Montes, Pedro | Hernández-Morales, Lucía | Monfil, Tomás | Espinosa-García, Claudia | Cervantes, Miguel

Article Type: Research Article

Abstract: Purpose: To assess the long-term neuroprotective effects of progesterone (P_{4} ) and allopregnanolone (ALLO) on functional and morphological parameters of the integrity of the hippocampus, after global cerebral ischemia. Methods: Adult male Sprague-Dawley rats were subjected to a transient severe (20 min) forebrain ischemia (Isch) episode and treated with P_4 or ALLO (8 mg/kg i.v.) or its vehicle, at 20 min, 2, 6, 24, 48 and 72 h after ischemia. Rats …subjected to Sham procedures, and intact rats were included as non-ischemic controls. Three months after ischemia, both the functional (spatial learning and memory, and reference and working memory), and the morphological integrity (dimensions of the hippocampal formation, thickness of the CA1 subfield, and pyramidal neuron population) of the hippocampus and the medial prefrontal cortex (mPFC) were determined. Results: Treatment with P_4 or ALLO significantly reduced the impairment in spatial learning and memory, as well as in reference and working memory, and prevented the narrowing of the hippocampus, otherwise induced by ischemia. This better performance of P_4 - and ALLO-treated rats than vehicle (Veh) -treated rats, occurred in spite of a loss of pyramidal neurons in the CA1, CA2, CA3 and hilus subfields of the Ammon's horn (remaining neurons: Isch+Veh: 21.0, 35.6, 44.1, and 40.3%; Isch+P_4 : 19.9, 32.2, 41.1, and 32.5%; Isch+ALLO: 25.5, 62.0, 73.7, and 56.7%), and non-significant changes in the mPFC, as compared to the Intact group (100%). Conclusions: Performance of P_4 - or ALLO-treated rats in learning and memory tests suggests that these steroids promoted neural conditions accounting for adequate functioning long after ischemia, in spite of the loss of hippocampal pyramidal neurons. Show more

Keywords: Neuroprotection, global cerebral ischemia, progesterone, allopregnanolone, long-term cognitive performance, hippocampal pyramidal neurons loss

DOI: 10.3233/RNN-2011-0571

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 1, pp. 1-15, 2011

Authors: Papadopoulos, Konstantinos I. | Low, Sharon Su Shing | Aw, Tar Choon | Chantarojanasiri, Teerachai

Article Type: Research Article

Abstract: Purpose: Cerebral palsy (CP) with a prevalence of 2.1 per 1,000 live births generates variable degrees of incurable developmental disability. The aim of the present report was to provide insight in the safety and feasibility of autologous umbilical cord blood (UCB) transfusion with low dose Granulocyte Colony Stimulating Factor (G-CSF) injections in improving the functional outcome of children with cerebral palsy. Methods: Two toddlers with diagnosed CP were given autologous umbilical cord blood (UCB) …transfusion accompanied by low dose subcutaneous granulocyte colony stimulating factor (G-CSF) injections. Results: Gross Motor Function Classification System (GMFCS) improvements were seen in both without any side effects being noted to date. Conclusion: In this first report, autologous UCB based intervention in tandem with low dose sc G-CSF administration seems to be feasible and safe with encouraging functional outcome improvements in children with CP. Show more

Keywords: Autologous cord blood stem cell transfusion, cerebral palsy, cord blood, granulocyte-colony stimulating factor, stem cells, umbilical cord, CD34+, Gross Motor Function Classification System, hypoxic-ischemic brain injury, neurogenesis, neuroprotection

DOI: 10.3233/RNN-2011-0572

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 1, pp. 17-22, 2011

Authors: Chauhan, Neelima B. | Gatto, Rodolfo

Article Type: Research Article

Abstract: Purpose: Traumatic brain injury (TBI) is a global health concern and growing socio-economic burden with limited treatment options. Behavioral assessment in experimental TBI with candidate therapeutic interventions is critical in order to expedite clinical translation. Statins constitute one of the potential treatment options based on their proven beneficial effects in various models of neurotrauma. We compared functional outcome after dietary intervention with representative hydrophilic Pravastatin or lipophilic Simvastatin and Lovastatin to test …if different statins will differentially affect cognitive outcomes after injury in a controlled cortical impact injury (CCI) mouse model of TBI. Methods: Mice were subjected to TBI with a controlled cortical impact produced on the left somatosensory-parietal cortex between bregma −1.82 and −2.06, fed with Simvastatin/Lovastatin/Pravastatin (2 mg/kg) for 8 weeks, evaluated for learning, memory and spontaneous exploration behavior followed by immunocytochemistry of an axonal marker. Results: Results indicate that feeding of TBI mice with Simvastatin and Lovastatin significantly improved spatial learning and memory, restored spontaneous exploration and restored axonal integrity (Simvastatin > Lovastatin). On the other hand, Pravastatin failed to improve spatial learning or memory or exploration or axonal damage. Conclusions: Current findings confirm maximum benefits rendered by Simvastatin and reinforce Simvastatin as the candidate therapy for treating TBI. Show more

Keywords: Traumatic brain injury, controlled cortical impact injury, simvastatin, lovastatin, pravastatin, spontaneous exploratory working memory, learning and memory, morris water maze, Y-maze

DOI: 10.3233/RNN-2011-0573

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 1, pp. 23-34, 2011

Authors: Szelag, Elzbieta | Szymaszek, Aneta | Aksamit-Ramotowska, Agnieszka | Fink, Martina | Ulbrich, Pamela | Wittmann, Marc | Pöppel, Ernst

Article Type: Research Article

Abstract: Purposes: The study sets the stage for temporal information processing as a fundamental basis of human cognition and a novel neurorehabilitation method. We focus on auditory perception of temporal order and address the following questions: (1) do subjects' age, gender, hearing status and cognitive functioning influence temporal ordering abilities; (2) are there any differences between Polish and German subjects on these abilities? Methods: 86 Polish and 82 German subjects aged from 20 to 69 years …were classified into 5 age groups. Subjects identified the order of two 1-ms clicks presented monaurally in rapid succession. The temporal order threshold (i.e. the minimum temporal gap required to report the stimulus order at 75% correctness) was assessed for each individual. Results: There were no differences between Polish and German subjects on temporal ordering. In both samples, a significant prolongation of temporal-order threshold was observed in subjects older than 60 years of age. Temporal processing was relatively resistant to subjects' hearing status, but it depended on cognitive competence. Thus, it is not chronological age as such but cognitive competence that may explain age-related decreases of temporal acuity. Furthermore, potential effects of age or gender are robust against the language background as no differences were observed between Polish and German subjects. Conclusions: We propose the existence of a neural mechanism underlying the perception of rapid changes in non-verbal acoustic features which constitute a frame for speech perception in many languages. This finding may be important with respect to future applications of temporal training in speech therapy programs designed for patients with receptive language disorders of different etiologies. Show more

Keywords: Cross-linguistic comparisons, time perception, cognitive function, temporal order, aging, hearing status

DOI: 10.3233/RNN-2011-0574

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 1, pp. 35-45, 2011

Authors: Fagerlund, Michael | Jaff, Nasren | Danilov, Alexandre I. | Peredo, Inti | Brundin, Lou | Svensson, Mikael

Article Type: Research Article

Abstract: Purpose: Cells in the ependymal region in the adult central nervous system (CNS) have been found to possess neural progenitor cell (NPC) like features including capacity for generating new neurons and glia in response to injury and inflammatory disease. Whether these cells are activated after a peripheral nerve injury has not previously been extensively evaluated. Methods: We investigate the possible activation and effect of NPCs in the ependymal region in the immediate vicinity to the hypoglossal nucleus in …the brainstem using two models of injuries, hypoglossal nerve transection and nerve avulsion after which the proliferation, migration and differentiation of ependymal regional NPCs were evaluated. Results: We showed that: (i) immunoreactivity for Sox2 was detected in cells in the ependymal region of the brainstem and that BrdU/Sox2-positive cells were observed after avulsion, but not after transection injury; (ii) avulsion induces re-expression of nestin in the ependymal layer as well as induced NPC migration from the ependymal layer; (iii) the chemokine SDF-1α (a marker for migrating cells) was upregulated ipsilateral to the nerve injury; (iiii) the NPCs migrating differentiated only into GFAP-positive astrocytes in the hypoglossal nucleus. Conclusion: These results suggest that nerve avulsion injury induces in parallel with the retrograde "axon reaction" activation of endogenous NPCs in the ependymal region and further suggest that these cells could be involved in repair and neuroregeneration after injury within the brainstem. Show more

Keywords: Ependymal cells, peripheral nerve injury, avulsion, astrocytes

DOI: 10.3233/RNN-2011-0578

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 1, pp. 47-59, 2011

Authors: Wali, Bushra | Sayeed, Iqbal | Stein, Donald G.

Article Type: Research Article

Abstract: Twenty-month-old male Fischer 344 rats with bilateral contusions of the frontal cortex (n=8/group) or sham operations received 16 mg/kg of progesterone or vehicle at 1 and 6 h post-injury, then once every 24 h for the next seven days, with tapering of the dose over the final two treatments. The rats' behavioral recovery was then evaluated on tests of locomotor activity and Morris water maze learning. All rats were sacrificed 21 days post-TBI and brains were …perfused and cryoprotected for necrotic cavity measurements. The injury produced significant impairments in activity and spatial learning compared to sham controls. The progesterone-treated rats had better functional outcomes than vehicle-treated rats with similar cortical injuries. The neurosteroid treatment did not affect the size of the necrotic cavity. Show more

Keywords: Aging, male rats, progesterone, recovery of function, traumatic brain injury

DOI: 10.3233/RNN-2011-0579

Citation: Restorative Neurology and Neuroscience, vol. 29, no. 1, pp. 61-71, 2011