In vitro studies on space-conforming self-assembling silk hydrogels as a mesenchymal stem cell-support matrix suitable for minimally invasive brain application.

Advanced cell therapies require robust delivery materials and silk is a promising contender with a long clinical track record. Our aim was to optimise self-assembling silk hydrogels as a mesenchymal stem cell (MSC)-support matrix that would allow future minimally invasive brain application. We used sonication energy to programme the transition of silk (1-5% w/v) secondary structure from a random coil to a stable ß-sheet configuration. This allowed fine tuning of self-assembling silk hydrogels to achieve space conformity in the absence of any silk hydrogel swelling and to support uniform cell distribution as well as cell viability. Embedded cells underwent significant proliferation over 14 days in vitro, with the best proliferation achieved with 2% w/v hydrogels. Embedded MSCs showed significantly better viability in vitro after injection through a 30G needle when the gels were in the pre-gelled versus post-gelled state. Silk hydrogels (4% w/v) with physical characteristics matching brain tissue were visualised in preliminary in vivo experiments to exhibit good space conformity in an ischemic cavity (intraluminal thread middle cerebral artery occlusion model) in adult male Sprague-Dawley rats (n = 3). This study informs on optimal MSC-hydrogel matrix conditions for minimally invasive application as a platform for future experiments targeting brain repair.

[Conditioning in resuscitated rats with originally different behavioral patterns].

Male white rats divided in three groups on the basis of their behavior in the elevated plus-maze were subjected to 10-min cardiac arrest. Analysis of the results of their subsequent food and active avoidance conditioning revealed the effects of the following factors: (1) a factor of initial typological features of the higher nervous activity, (2) a factor of general brain mechanisms of postresuscitation, and (3) a factor of postresuscitation features in rats with different behaviors, which represented changes in different mechanisms of conditioned reflex performance in these animals.

[Postresuscitation cerebral structural and functional changes associated with the initial type of behavior]. / Postreamanitsionnye strukturno-funktsional'nye izmeneniia mozga, sopriazhennye s iskhodnym tipom povedeniia.

The elevated cross-shaped labyrinth test carried out on highly, moderately, and low active experimental animals revealed significant differences in the baseline density and composition of neuroglial populations of numerous formations of the brain, as well as in the early structural and functional sequels of experienced clinical death. The most pronounced postresuscitation abnormal changes were observed in highly active animals and the least marked ones were seen in moderately active animals.

[Development of postresuscitation morphological changes of hippocampal and cerebellar neurons: common regularities and specific features]. / Razvitie postreanimatsionnykh morfologicheskikh izmenenii neironov gippokampa i mozzhechka: obshchie zakonomernosti i osobennosti.

A comparative morphometric study of postresuscitation changes in the neuronal populations of the pyramidal cells from hyppocampal sector CA1 and Purkinje cells of the lateral cerebellar region in the course of postresuscitation period after 12-minute cardiac arrest in rats has shown that the changes differ in severity and pattern. In the pyramidal cells there were reversible dystrophic alterations of the neurons. Purkinje cells showed death of some neurons, this process progressed in the course of postresuscitation period. A positive effect of the peptide kyotorphin on the brain condition after resuscitation was found but its efficacy in different neuronal populations varied.

[Effect sandostatin on functional and structural recovery of the central nervous system after clinical death]. / Vliianie sandostatina na funktsional'no-strukturnoe vosstanovlenie tsentral'noi nervnoi sistemy posle klinicheskoi smerti.

A behavior examination set was used to reveal a decreased anxiety as well as increased locomotor and exploratory activities and changes in resuscitated animals undergoing different learning tests. A single injection of sandostatin--an analogue of regulatory peptide somatostatin--was found to improve the structural and functional recovery of the central nervous system after a 12-minute cardiac arrest.

Postresuscitation recovery of functional activity of central nervous system in rats during combination treatment with mexidol and neuropeptides delta sleep-inducing peptide and oxytocin.

In experiments on rats we studied the effects of antioxidant and membrane-protecting agent mexidol and neuropeptides delta sleep-inducing peptide and oxytocin administered during resuscitation after 12-min clinical death. Individual and combination treatment with these substances accelerated recovery of the neurological status and partially or completely corrected behavioral disorders associated with changes in the emotional and motivational status. Combined administration of mexidol and oxytocin most significantly promoted postresuscitation recovery of functional activity in the central nervous system.

[Therapy of postresuscitation behavioral disorders with mexidol and kyotorphin]. / Korrektsiia postreanimatsionnykh narushenii povedencheskikh reaktsii meksidolom i kiotorfinom.

A complex of behavioral tests revealed diminished anxiety, increased locomotor and exploratory activities, and changes in different learning tests in resuscitated animals. Mexidol alone and in combination with kyotorphin exhibited antistressogenic and nootropic activities, and led to a compensation of ischemic lesions in rats. It can be stated that a the injection of mexidol in combination with kyotorphin yielded better results due to its neuroprotective effect in the CA1 and CA4 fields of the hippocampus.