Targeted thrombolysis strategies for neuroprotective effect

Stroke is usually treated by systemic thrombolytic therapy if the patient presents within an appropriate time window. There is also widespread interest in the development of thrombolytic agents that can be used in cases of delayed presentation. Current agents that can be used in cases of delayed presentation of nerve damage by thrombus. Current systemic thrombolytic therapy is associated with adverse effects such as fibrinogenolysis and bleeding. In an attempt to increase the efficacy, safety, and specificity of thrombolytic therapy, a number of targeted thrombolytic agents have been studied in recent years. This review focuses on the concepts underlying targeted thrombolytic therapy and describes recent drug developments in this field.     

Green tea polyphenols protect spinal cord neurons against hydrogen peroxide-induced oxidative stress

Green tea polyphenols are strong antioxidants and can reduce free radical damage. To investigate their neuroprotective potential, we induced oxidative damage in spinal cord neurons using hydrogen peroxide, and applied different concentrations(50–200 μg/mL) of green tea polyphenol to the cell medium for 24 hours. Measurements of superoxide dismutase activity, malondialdehyde content, and expression of apoptosis-related genes and proteins revealed that green tea polyphenol effectively alleviated oxidative stress. Our results indicate that green tea polyphenols play a protective role in spinal cord neurons under oxidative stress.     

In the presence of danger：the extracellular matrix defensive response to central nervous system injury

Glial cells in the central nervous system （CNS） contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient on and axon potential propagation. In the normal adult CNS, the extracellular matrix （ECM） is relatively stable except in selected regions characterized by dynamic remodeling. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/ central nervous system border. An advantage of this response is to limit the invasion of damaging cells and diffusion of toxic molecules into the spared tissue regions, but this occurs at the cost of inhibiting migration of endogenous repair cells and preventing axonal regrowth. The following review was prepared by reading and discussing over 200 research articles in the field published in PubMed and selecting those with significant impact and/or controversial points. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury. Current research strategies directed at modifying the inhibitory perilesion microenvironment without eliminating the protective functions of glial cell activation are discussed.     

Analgesic effect of intrathecal bumetanide is accompanied by changes in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain

Accumulating evidence has demonstrated that the sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 have a role in the modulation of pain transmission at the spinal level through chloride regulation in the pain pathway and by effecting neuronal excitability and pain sensitization. The present study aimed to investigate the analgesic effect of the speciifc sodium-potassium-chloride co-transporter 1 inhibitor bumetanide, and the change in spinal sodium-potassium-chloride co-transporter 1 and potassium-chloride co-transporter 2 expression in a rat model of incisional pain. Results showed that intrathecal bumetanide could decrease cumulative pain scores, and could increase thermal and mechanical pain thresholds in a rat model of incisional pain. Sodium-potassium-chloride co-transporter 1 expression in-creased in neurons from dorsal root ganglion and the deep laminae of the ipsilateral dorsal horn following incision. By contrast, potassium-chloride co-transporter 2 expression decreased in neurons of the deep laminae from the ipsilateral dorsal horn. These ifndings suggest that spinal sodium-potassium-chloride co-transporter 1 expression was up-regulated and spinal potassi-um-chloride co-transporter 2 expression was down-regulated following incision. Intrathecal bumetanide has analgesic effects on incisional pain through inhibition of sodium-potassi-um-chloride co-transporter 1.     

The Effect of Electrode Placement and Interphase Interval on Force Production During Stimulation of the Dorsiflexor Muscles

The aims of this study were to investigate whether introducing an interphase interval (IPI) to biphasic pulses during stimulation of the dorsiflexor muscles would affect force production and to determine whether the IPI effect is dependent on electrode position. Twelve healthy volunteers participated in the study. Each subject participated in one session during which electrically induced contraction (EIC) forces of the ankle dorsiflexors were measured with five different IPI settings ranging from 0 to 400 μs. Forces of EICs were assessed with the electrodes placed either with the proximal electrode positioned over the common peroneal nerve and the second electrode over the dorsiflexor muscles or with both electrodes located over the dorsiflexor muscles. The order of electrode placements and of the different IPI settings was randomized across subjects. The results indicated that the introduction of a 100‐μs‐long IPI may enhance force production when one electrode is located over the common peroneal nerve. However, increasing the duration of the IPI beyond 100 μs did not result in further increase in force production. In contrast, the introduction of an IPI did not increase force production when both electrodes were located over the dorsiflexor muscles. These findings may help to optimize stimulation settings during functional electrical stimulation to prevent foot‐drop.     

Asymptomatic Penetration of the Oculomotor Nerve by a De Novo Aneurysm Associated with Severe Atherosclerotic Stenosis of the Supraclinoid Internal Carotid Artery

A 70-year-old woman presented with headaches and recurrent stroke symptoms. During five years, the patient has been treated for cerebral infarction associated with severe atherosclerotic stenosis of the internal carotid artery. Three-year follow-up magnetic resonance angiography showed a tiny de novo aneurysm arising from the distal part of atherosclerotic internal carotid artery. And 5-year follow-up three-dimensional CT angiogram demonstrated a definite aneurysm enlargement as large as requiring treatment. During dissection of aneurysm, the oculomotor nerve was found to be penetrated with the growing de novo aneurysm. The authors report a case of a de novo aneurysm, which resulted from atherosclerotic stenosis of the internal carotid artery at the supraclinoid portion, that was found to be penetrating the oculomotor nerve with no ocular palsy.