Perspectives on weak interactions in complex materials at different length scales.

Nanocomposite materials consist of nanometer-sized quantum objects such as atoms, molecules, voids or nanoparticles embedded in a host material. These quantum objects can be exploited as a super-structure, which can be designed to create material properties targeted for specific applications. For electromagnetism, such targeted properties include field enhancements around the bandgap of a semiconductor used for solar cells, directional decay in topological insulators, high kinetic inductance in superconducting circuits, and many more. Despite very different application areas, all of these properties are united by the common aim of exploiting collective interaction effects between quantum objects. The literature on the topic spreads over very many different disciplines and scientific communities. In this review, we present a cross-disciplinary overview of different approaches for the creation, analysis and theoretical description of nanocomposites with applications related to electromagnetic properties.

Optimizing Manufacturing and Osseointegration of Ti6Al4V Implants through Precision Casting and Calcium and Phosphorus Ion Implantation? In Vivo Results of a Large-Scale Animal Trial.

BACKGROUND: Uncemented implants are still associated with several major challenges, especially with regard to their manufacturing and their osseointegration. In this study, a novel manufacturing technique-an optimized form of precision casting-and a novel surface modification to promote osseointegration-calcium and phosphorus ion implantation into the implant surface-were tested in vivo. METHODS: Cylindrical Ti6Al4V implants were inserted bilaterally into the tibia of 110 rats. We compared two generations of cast Ti6Al4V implants (CAST 1st GEN, n = 22, and CAST 2nd GEN, n = 22) as well as cast 2nd GEN Ti6Al4V implants with calcium (CAST + CA, n = 22) and phosphorus (CAST + P, n = 22) ion implantation to standard machined Ti6Al4V implants (control, n = 22). After 4 and 12 weeks, maximal pull-out force and bone-to-implant contact rate (BIC) were measured and compared between all five groups. RESULTS: There was no significant difference between all five groups after 4 weeks or 12 weeks with regard to pull-out force (p > 0.05, Kruskal Wallis test). Histomorphometric analysis showed no significant difference of BIC after 4 weeks (p > 0.05, Kruskal-Wallis test), whereas there was a trend towards a higher BIC in the CAST + P group (54.8% ± 15.2%), especially compared to the control group (38.6% ± 12.8%) after 12 weeks (p = 0.053, Kruskal-Wallis test). CONCLUSION: In this study, we found no indication of inferiority of Ti6Al4V implants cast with the optimized centrifugal precision casting technique of the second generation compared to standard Ti6Al4V implants. As the employed manufacturing process holds considerable economic potential, mainly due to a significantly decreased material demand per implant by casting near net-shape instead of milling away most of the starting ingot, its application in manufacturing uncemented implants seems promising. However, no significant advantages of calcium or phosphorus ion implantation could be observed in this study. Due to the promising results of ion implantation in previous in vitro and in vivo studies, further in vivo studies with different ion implantation conditions should be considered.

Dual effect of serotonin on the dendritic growth of cultured hippocampal neurons: Involvement of 5-HT1A and 5-HT7 receptors.

Serotonin acts through its receptors (5-HTRs) to shape brain networks during development and modulates essential functions in mature brain. The 5-HT1AR is mainly located at soma of hippocampal neurons early during brain development and its expression gradually shifts to dendrites during postnatal development. The 5-HT7R expressed early during hippocampus development, shows a progressive reduction in its expression postnatally. Considering these changes during development, we evaluated in cultured hippocampal neurons whether the 5-HT1AR and 5-HT7R change their expression, modulate dendritic growth, and activate signaling pathways such as ERK1/2, AKT/GSK3ß and LIMK/cofilin, which may sustain dendrite outgrowth by controlling cytoskeleton dynamics. We show that mRNA levels of both receptors increase between 2 and 7 DIV; however only protein levels of 5-HT7R increase significantly at 7 DIV. The 5-HT1AR is preferentially distributed in the soma, while 5-HT7R displays a somato-dendritic localization at 7 DIV. Through stimulation with 5-HT at 7 DIV during 24h and using specific antagonists, we determined that 5-HT1AR decreases the number of primary and secondary dendrites and restricts the growth of primary dendrites. The activation of 5-HT1AR and 5-HT7R promotes the growth of short secondary dendrites and triggers ERK1/2 and AKT phosphorylation through MEK and PI3K activation respectively; without changes in the phosphorylation of LIMK and cofilin. We conclude that 5-HT1AR restricts dendritogenesis and outgrowth of primary dendrites, but that both 5-HT1AR and 5-HT7R promote secondary dendrite outgrowth. These data support the role of 5-HT in neuronal outgrowth during development and provide insight into cellular basis of neurodevelopmental disorders.

Novel aspects of glucocorticoid actions.

Normal hypothalamic-pituitary-adrenal (HPA) axis activity leading to the rhythmic and episodic release of adrenal glucocorticoids (GCs) is essential for body homeostasis and survival during stress. Acting through specific intracellular receptors in the brain and periphery, GCs regulate behaviour, as well as metabolic, cardiovascular, immune and neuroendocrine activities. By contrast to chronic elevated levels, circadian and acute stress-induced increases in GCs are necessary for hippocampal neuronal survival and memory acquisition and consolidation, as a result of the inhibition of apoptosis, the facilitation of glutamatergic neurotransmission and the formation of excitatory synapses, and the induction of immediate early genes and dendritic spine formation. In addition to metabolic actions leading to increased energy availability, GCs have profound effects on feeding behaviour, mainly via the modulation of orexigenic and anorixegenic neuropeptides. Evidence is also emerging that, in addition to the recognised immune suppressive actions of GCs by counteracting adrenergic pro-inflammatory actions, circadian elevations have priming effects in the immune system, potentiating acute defensive responses. In addition, negative-feedback by GCs involves multiple mechanisms leading to limited HPA axis activation and prevention of the deleterious effects of excessive GC production. Adequate GC secretion to meet body demands is tightly regulated by a complex neural circuitry controlling hypothalamic corticotrophin-releasing hormone (CRH) and vasopressin secretion, which are the main regulators of pituitary adrenocorticotrophic hormone (ACTH). Rapid feedback mechanisms, likely involving nongenomic actions of GCs, mediate the immediate inhibition of hypothalamic CRH and ACTH secretion, whereas intermediate and delayed mechanisms mediated by genomic actions involve the modulation of limbic circuitry and peripheral metabolic messengers. Consistent with their key adaptive roles, HPA axis components are evolutionarily conserved, being present in the earliest vertebrates. An understanding of these basic mechanisms may lead to novel approaches for the development of diagnostic and therapeutic tools for disorders related to stress and alterations of GC secretion.

MicroRNA-based therapy in cardiology.

The pathogenic role of noncoding microRNA (miR, miRNA) has been demonstrated for several disease conditions in the heart. The underlying molecular mechanisms have been deciphered for numerous miRs that are deregulated as a result of cardiac stress. Innovative therapeutic strategies based on antifibrotic, antihypertrophic, or proangiogenic effects of miRNAs are being currently developed to improve the function of the failing heart. Identifying a safe and efficient miR-based strategy remains challenging, yet these novel approaches offer enormous potential for the treatments for heart failure. In this review we highlight the latest development in the cardiac miRNA field.

[The current technical possibilities of the peroperative safety advancement in the microsurgery of cerebral aneurysms - a review article]. / Soucasné technické moznosti zvýsení peroperacní bezpecnosti pri mikrochirurgii mozkových aneuryzmat - souhrnný referát.

The authors present the technical aspects of perioperative safety during the microsurgery of cerebral aneurysms. We evaluated the advantages and disadvantages of the microvascular Doppler ultrasonography, the intraoperative digital subtraction angiography, the intraoperative transit time flowmetry, the intraoperative monitoring - motor evoked potentials and somatosensory evoked potentials, and the ICG videoangiography. The authors, based on their own experience, recommend combining different methods to eliminate the weak points of the individual specific methods. Combining the ICG with the flowmetry and the motor evoked potentials enhances safety during the surgery of cerebral aneurysms with the resultant reduction of the perioperative morbidity/mortality.

Effect of exercise on circulating levels of brain-derived neurotrophic factor (BDNF) in overweight and obese subjects.

Exercise increases the expression of brain-derived neurotrophic factor (BDNF) in rodents and in healthy humans. Its relationship with weight loss and improvement in metabolic parameters, in obese human subjects, has not been elucidated. The aim of the study was to evaluate the effect of an aerobic exercise program on circulating levels of BDNF in overweight and obese subjects. We measured anthropometric and metabolic parameters in 15 male and female nondiabetic outpatients (age 38.3±9.5 years, BMI 27-35 kg/m2), before and after 30 sessions of aerobic exercise (3 sessions per week). Plasma (p), serum (s), and platelet (plat) BDNF concentrations were measured at basal condition and after completing 15 and 30 sessions of exercise. Subjects were advised to continue their usual food intake. A significant decrease in weight, BMI, waist circumference, diastolic blood pressure and total cholesterol was observed at the end of the study (p<0.02). Serum and platBDNF showed a significant increase during the training period (p=0.005 and 0.04 respectively). However, pBDNF showed no significant increase. Area under the curve of glucose at baseline, was inversely correlated with sBDNF (r= - 0.53, p=0.04) and platBDNF (r= - 0.6, p=0.01) after session 15. Also, platBDNF was correlated inversely with post load insulin and HOMA2-IR at the end of the training program (r= - 0.53, p=0.03 and r= - 0.52, p=0.04, respectively). In overweight and obese subjects, serum and platBDNF levels increase after 30 sessions of aerobic exercise. This is accompanied with the improvement of anthropometric and metabolic parameters and modest weight loss.

[Patent foramen ovale and the risk of paradoxical embolization of venous bubbles in divers - cave for foam sclerotization of varicose veins]. / Perzistence foramen ovale patens a riziko paradoxní embolizace zilních bublin u potápecu - cave pro sklerotizaci varixu penovou metodou.

INTRODUCTION: Foam sclerotization of varicose veins may cause paradoxical embolization through patent foramen ovale (PFO). The aim of our study was to: 1) select an optimal screening method for the detection of PFO; 2) determine the prevalence of PFO in a non-selected population; and 3) test the risk of paradoxical embolization of venous bubbles in patients with PFO. MATERIALS AND METHODS: A diver after decompression is a suitable model for determining the risk of paradoxical embolization of venous gas bubbles. 329 Czech divers were screened for PFO. In a pilot study, we compared Transcranial Doppler Sonography (TCD) with Transesophageal Echocardiography (TEE) in 100 patients. TCD alone was used for further screening. In 31 divers with PFO, nitrogen bubbles were detected after simulated dives. Transthoracic Echocardiography (TTE) was used to detect venous bubbles in right-sided heart chambers; TTE and TCD were used to detect arterial bubbles. The right-to-left shunt was rated as non-significant (<20 arterial bubbles) or significant (20 arterial bubbles). Different decompression regimens were compared. RESULTS: In the pilot study, TCD was compared with the gold standard in PFO detection - TEE. The negative predictive value of TCD was 100%, positive predictive value was 92%. Screening was performed in a total of 329 divers, PFO was detected in 85 (25%), significant R-L shunt in 45 (14%). In simulated dive to 50 m maximum depth, venous nitrogen bubbles were detected in 7/8 (88%) divers. In 6/8 (75%) divers, paradoxical embolization was confirmed - nitrogen bubbles were detected in the systemic circulation. CONCLUSION: PFO prevalence with significant R-L shunt was 14% in the non-selected population of Czech divers. Simulated dives indicate that PFO represents a risk factor for paradoxical embolization of gas bubbles. TCD is a suitable screening method for the detection of PFO and the evaluation of R-L shunt significance. These results are indicative of a possible high risk of paradoxical embolization of gas bubbles and the trombogenic substance in patients with a larger PFO and significant R-L shunt undergoing foam sclerotization of varicose veins.

Sex, stress, and mood disorders: at the intersection of adrenal and gonadal hormones.

The risk for neuropsychiatric illnesses has a strong sex bias, and for major depressive disorder (MDD), females show a more than 2-fold greater risk compared to males. Such mood disorders are commonly associated with a dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence of MDD may be related with the levels of gonadal steroid hormone in adulthood or during early development as well as with the sex differences in HPA axis function. In rodents, organizational and activational effects of gonadal steroid hormones have been described for the regulation of HPA axis function and, if consistent with humans, this may underlie the increased risk of mood disorders in women. Other developmental factors, such as prenatal stress and prenatal overexposure to glucocorticoids can also impact behaviors and neuroendocrine responses to stress in adulthood and these effects are also reported to occur with sex differences. Similarly, in humans, the clinical benefits of antidepressants are associated with the normalization of the dysregulated HPA axis, and genetic polymorphisms have been found in some genes involved in controlling the stress response. This review examines some potential factors contributing to the sex difference in the risk of affective disorders with a focus on adrenal and gonadal hormones as potential modulators. Genetic and environmental factors that contribute to individual risk for affective disorders are also described. Ultimately, future treatment strategies for depression should consider all of these biological elements in their design.

MicroRNA-based therapeutic approaches in the cardiovascular system.

MicroRNAs (miRNAs) are endogenous small ribonucleotides that participate in the orchestration of the genome by regulating target messenger RNA translation. MiRNAs control physiological processes and misexpression of miRNAs is pathogenically involved in many diseases including cardiovascular diseases. Normalization of miRNA expression and thus downstream target networks may have enormous therapeutic chances but also risks. We here highlight and discuss recent advances in the development and use of miRNA therapeutics to target miRNAs in vivo that may translate into novel therapeutic strategies for cardiovascular diseases in the future.

[Current microsurgical and neurointerventional therapy of cerebral aneurysms]. / Soucasná mikrochirurgická a neurointervencní terapie mozkových aneuryzmat.

Cerebral aneurysms occur in 5% of the adult population. Their most severe clinical manifestation is subarachnoid haemorrhage occurring in half of the patients. Morbidity and mortality of subarachnoid hemorrhage is relatively high. Stopping blood flow into the aneurysmal sac is the treatment objective. The basic techniques to achieve this are closing the aneurysmal neck with a clip - clipping - and the induction of intraaneurysmal thrombosis using platinum coils - coiling. Fusiform and giant aneurysms represent a technical challenge. The solution for indicated cases is the occlusion of the magistral artery along with a high-flow bypass. A new option is the use of special stents - flow-diverters - in unruptured aneurysms. The authors present the current view on the treatment of both ruptured and unruptured aneurysms. At the same time the authors focus on factors that influence the application of up-to-date knowledge on everyday activities in their departments.

Identification of cardiovascular microRNA targetomes.

MicroRNAs (miRNAs) are strong post-transcriptional regulators targeting multiple targets. Endogenously transcribed, miRNAs specifically bind to complementary sequences of mRNAs and repress their expression thus govern control of cellular signaling pathways. An altered miRNA expression is causally related to cardiovascular disease. Identification of miRNA-dependent pathways is therefore an important aim to develop new therapeutic approaches. To understand miRNA function in various cardiovascular cells, the identification of individual miRNA target genes is of utmost importance. Indeed, the biological function of a miRNA is dependent on the availability of potential targets in a cell. We here summarize and discuss current challenging approaches to identify miRNA targetomes which will help to understand miRNA function in cardiac homeostasis and disease.

Urinary miR-210 as a mediator of acute T-cell mediated rejection in renal allograft recipients.

MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. Circulating miRNAs are remarkably stable in the blood. We tested whether miRNAs are also detectable in urine and may serve as new predictors of outcome in renal transplant patients with acute rejection. We profiled urinary miRNAs of stable transplant patients and transplant patients with acute rejection. The miR-10a, miR-10b and miR-210 were strongly deregulated in urine of the patients with acute rejection. We confirmed these data in urine of a validation cohort of 62 patients with acute rejection, 19 control transplant patients without rejection and 13 stable transplant patients with urinary tract infection by quantitative RT-PCR. The miR-10b and miR-210 were downregulated and miR-10a upregulated in patients with acute rejection compared to controls. Only miR-210 differed between patients with acute rejection when compared to stable transplant patients with urinary tract infection or transplant patients before/after rejection. Low miR-210 levels were associated with higher decline in GFR 1 year after transplantation. Selected miRNAs are strongly altered in urine of the patients with acute renal allograft rejection. The miR-210 levels identify patients with acute rejection and predict long-term kidney function. Urinary miR-210 may thus serve as a novel biomarker of acute kidney rejection.

[Simultaneous carotid endarterectomy and coronary revascularization: indications and results]. / Simultánní karotická endarterektomie a koronární revaskularizace: indikace a výsledky.

AIM: Evaluation of operative results and complications in high-risk patients who underwent combined carotid and coronary revascularization. PATIENTS AND METHODS: Combined operation--carotid endarterectomy (CEA) and coronary artery bypass graft (CABG) was performed in the period 2000-2009 in 68 patients. Simultaneous operation was indicated in patients with unstable angina pectoris and 1. symtomatic internal carotid artery (ICA) stenosis > or = 50%, or 2. bilateral asymptomatic ICA stenosis > or = 60% or 3. asymptomatic ICA stenosis > or = 60% combined with contralateral ICA occlusion. Combined operations represented 5.8% of whole CEA series. Mean age was 69.9 (51-82) years, men were 46, women 22. Carotid angiography proved unilateral (always symptomatic) ICA stenosis in 25 patients, bilateral ICA stenosis in 35 patients and ICA stenosis combined with contralateral carotid occlusion in 8 patients. Neurological preoperative symptomatology: TIA was present in u 20 patients, minor stroke in 6 and major stroke in 5 patients. 37 patients were asymptomatic. One CABG was performed in 5 patients, 2 CABG in 20 patients, 3 CABG in 19 patients and 4 CABG in 6 patients. The rest of 18 patients had CABG operation combined with valve procedure. Comorbidity: hypertension 100%, diabetes mellitus 57.3%, hyperlipidemia 60.3%. Shunt was selectively used in 4.4%. The need for shunt was established using back stump pressure and near infrared spectroscopy. RESULTS: Mortality was 8.8% (6/68). The cause of death were multiorgan failure in two cases, ipsilateral stroke in two patients, respiratory insufficiency and cardiac failure due to graft occlusion both in one patient. Good recovery was recorded in 91.2%. CONCLUSION: Combined carotid and coronary revascularization has acceptable neurological morbidity/mortality in high risk patients. Strict requirement is thorough selection of patients.

The (-765 G→C) promoter variant of the COX-2/PTGS2 gene is associated with a lower risk for end-stage hip and knee osteoarthritis.

BACKGROUND: Functional polymorphisms in genes of proinflammatory signalling cascades may contribute to the genetic risk of osteoarthritis (OA). OBJECTIVE: To examine a possible association between end-stage OA of the hip and knee joint and a known single nucleotide polymorphism (SNP) of the COX-2 gene promoter. METHODS: The SNP -765 G→C (rs20417) of the COX-2 gene promoter was genotyped by pyrosequencing in 531 (320 women/211 men) patients with OA from the Ulm Osteoarthritis Study and 400 (200 women/200 men) regional controls from the south-west of Germany. RESULTS: In the whole study population the C allele was associated with a lower risk (per allele OR 0.57; 95% CI 0.43 to 0.75, p<0.0001) and the G allele with a higher risk for end-stage OA. Analysis of subgroups confirmed this result for primary, bilateral, hip and knee OA. CONCLUSION: The promoter polymorphism rs20417 of the COX-2 gene contributes to the genetic risk for end-stage hip and knee OA.

Endarterectomy for asymptomatic carotid artery stenosis under local anaesthesia.

BACKGROUND: In this article, we present our experience with such operations performed under local anaesthesia. METHODS: From January 1997 to November 2007, there were 387 patients operated on for asymptomatic carotid stenosis. Patient data were retrospectively evaluated. Thirty-day neurological morbidity and mortality from six different subgroups were analysed and compared. The numbers of perioperative transient ischaemic attacks, as well as surgical and other perioperative complications were also evaluated. RESULTS: Overall morbidity and mortality was 1.8% (seven patients). Stroke was noted in 1.3% (five patients). Transitory ischaemic attacks within the first 30 days were observed in 1.6% (six patients). Only those patients who had intraluminal shunt insertion were found to have significantly higher morbidity and mortality. (p = 0.000018). Myocardial infarction was observed in 0.5% (two patients), one fatal. CONCLUSION: We have achieved acceptable morbidity and mortality rates (1.8%) according to the parameters set by previous studies such as Asymptomatic Carotid Atherosclerosis Study and Asymptomatic Carotid Stenosis Trial as well as American Heart Association and European Stroke Organisation guidelines. All surgeries were done under local anaesthesia. Shunts were inserted in 22 cases (5.68%).

Comparison of the antidepressant sertraline on differential depression-like behaviors elicited by restraint stress and repeated corticosterone administration.

Depressive disorder involves emotional, cognitive, autonomic and endocrine alterations and also evidences support the role of stress in the development of this disorder. Because the hypothalamic-pituitary-adrenal axis is involved in the stress response with a concomitant rise in plasma corticoids, the present study compares the antidepressant effects of sertraline (10mg/kg, i.p.) on behavioral changes elicited by (i) restraint stress (2.5h/day for 13days) and (ii) corticosterone injections (30mg/kg, s.c., for 13days). Stressed animals, but not corticosterone-treated animals displayed anxiety behavior and a reduction in the acquisition of a conditioned avoidance response to 25% of control levels (8.0±2.2 vs. 31.7±3.2), being this effect partly sensitive to sertraline. Stressed, but not corticosterone-treated, animals displayed an increased escape failure compared with the control group (24.6%±3.5 vs. 1.6±0.7), an effect partly prevented by sertraline treatment (7.3%±2.0). Both stressed rats and corticosterone-treated rats showed an increase in immobility in the forced swim test, an effect prevented by sertraline. These results suggest that the altered behaviors elicited by stress and corticosterone can be explained by neural modifications that are sensitive to the sertraline antidepressant.

[Spinal cord stab injury associated with modified Brown-Séquard syndrome symptoms--a case review and literature overview]. / Bodné poranení míchy s projevy modifikovovaného Brown-Séquardova syndromu--kazuistika a prehled literatury.

Authors present case-report of young man with incomplete spinal cord injury after penetrating stab wound. Knife blade entered the skin in the level C3/4 in the back of the neck and directed to the right and downward. Both dorsal spinal cord columns and right half of spinal cord were transected. Neurological presentation was Brown-Séquard syndrome combined with dorsal columns syndrome. Wound revision was performed followed by dural closure. 18 month after injury significant neurological improvement of right hemiparesis was recorded and the patient is self-sufficient. Spinal cord stab wounds are rare. Typical clinical symptomatology is incomplete spinal cord injury. Clinical improvement of Brown-Séquard syndrome in our patient entirely corelates with literature.

Altered migration and adhesion potential of pro-neurally converted human bone marrow stromal cells.

BACKGROUND: Bone marrow (BM)-derived mesenchymal stromal cells (MSC) are promising candidate cells for the development of neuroregenerative therapies. We have previously introduced the pro-neural conversion of human MSC to neural stem cell-like cells (m-NSC) by culturing them in suspension culture under serum-free conditions. METHODS: In the present study, we used a modified Boyden chamber assay to study the influence of various chemoattractants and extracellular matrix components on MSC and m-NSC migration in vitro. The underlying mechanisms were investigated further by applying real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) and flow cytometry. RESULTS: The basal migration of m-NSC was significantly reduced compared with MSC (six versus 27 out of 10,000 cells migrated within 6 h). We evaluated the effects of bone morphogenic protein 2 (BMP2), insulin-like growth factor 1 (IGF1), platelet-derived growth factor bb (PDGFbb), vascular endothelial growth factor (VEGFa), and stromal cell-derived factor 1 (SDF1) on the migration potential of both cell types and PDGFbb proved to be the most potent stimulant of migration (235 versus 198 m-NSC or MSC migrated). Adhesion of m-NSC to the filter membrane was delayed and not affected by IGF1 or PDGFbb: 90% of MSC, but only 20% of m-NSC, adhered within 1 h, with 90% of m-NSC adhering within 3 h. However, real-time RT-PCR and flow cytometry revealed an up-regulation of the PDGF receptor B following conversion. Coating the membranes with collagen type I or hyaluronan also significantly influenced cell migration. DISCUSSION: We could identify major chemoattractive factors for m-NSC and gained partial insight into the complex processes involved in migration of neurally converted cells.

Plasticity of hippocampus following perinatal asphyxia: effects on postnatal apoptosis and neurogenesis.

Asphyxia during delivery produces long-term deficits in brain development, including hippocampus. We investigated hippocampal plasticity after perinatal asphyxia, measuring postnatal apoptosis and neurogenesis. Asphyxia was performed by immersing rat fetuses with uterine horns removed from ready-to-deliver rats into a water bath for 20 min. Caesarean-delivered pups were used as controls. The animals were euthanized 1 week or 1 month after birth. Apoptotic nuclear morphology and DNA breaks were assessed by Hoechst and TUNEL assays. Neurogenesis was estimated by bromodeoxyuridine/MAP-2 immunocytochemistry, and the levels and expression of proteins related to apoptosis and cell proliferation were measured by Western blots and in situ hybridization, respectively. There was an increase of apoptosis in CA1, CA3, and dentate gyrus (DG) and cell proliferation and neurogenesis in CA1, DG, and hilus regions of hippocampus 1 week after asphyxia. The increase of apoptosis in CA3 and cell proliferation in the suprapyramidal band of DG was still observed 1 month following asphyxia. There was an increase of BAD, BCL-2, ERK2, and bFGF levels in whole hippocampus and bFGF expression in CA1 and CA2 and hilus at P7 and P30. There was a concomitant decrease of phosphorylated-BAD (Ser112) levels. The increase of BAD levels supports the idea of delayed cell death after perinatal asphyxia, whereas the increases of BCL-2, ERK2, and bFGF levels suggest the activation of neuroprotective and repair pathways. In conclusion, perinatal asphyxia induces short- and long-term regionally specific plastic changes, including delayed cell death and neurogenesis, involving pro- and antiapoptotic as well as mitogenic proteins, favoring hippocampal functional recovery.