Intravenous thrombolysis for ischemic stroke in the Veneto region: the gap between eligibility and reality

Journal of Thrombosis and Thrombolysis - Intravenous thrombolysis (IVT) is the treatment of choice for most patients with acute ischemic stroke. According to the recently updated guidelines, IVT...     

Transplantation of rat synapsin-EGFP-labeled embryonic neurons into the intact and ischemic CA1 hippocampal region: distribution, phenotype, and axodendritic sprouting

A major limitation of neural transplantation studies is assessing the degree of host-graft interaction. In the present study, rat hippocampal/cortical embryonic neurons (E18) were infected with a lentivirus encoding enhanced green fluorescent protein (GFP) under control of the neuron-specific synapsin promoter, thus permitting robust identification of labeled neurons after in vivo grafting. Two weeks after transient forebrain ischemia or sham-surgery, GFP-expressing neurons were transplanted into CA1 hippocampal regions in immunosuppressed adult Wistar rats. The survival, distribution, phenotype, and axonal projections of GFP-immunoreactive (IR) positive transplanted neurons were evaluated in the sham-operated and ischemia- damaged CA1 hippocampal regions 4, 8, and 12 weeks after transplantation. In both experimental groups, we observed that the main phenotype of host-derived afferents projecting towards grafted GFP-IR neurons as well as transplant-derived GFP-IR efferents were glutamatergic in both animal groups. GFP axonal projections were seen in the nucleus accumbens, septal nuclei, and subiculum-known target areas of CA1 pyramidal neurons. Compared to sham-operated animals, GFP-IR neurons grafted into the ischemia-damaged CA1 migrated more extensively throughout a larger volume of host tissue, particularly in the stratum radiatum. Moreover, enhanced axonal sprouting and neuronal plasticity of grafted cells were evident in the hippocampus, subiculum, septal nuclei, and nucleus accumbens of the ischemia-damaged rats. Our study suggests that the adult rat brain retains some capacity to direct newly sprouting axons of transplanted embryonic neurons to the correct targets and that this capacity is enhanced in previously ischemia-injured forebrain.     

Neurological complications of tick borne encephalitis: the experience of 89 patients studied and literature review

Tick borne encephalitis (TBE) is an acute febrile syndrome that can be complicated with neurological symptoms ranging from mild meningitis to severe encephalomyelitis. The causative agent is a virus belonging to the family of flaviviruses. We have collected a series of 89 patients and compared the clinical course with the main data of the literature of TBE. This review in addition describes the clinical manifestations associated with TBE infections, the main molecular-biological properties of these viruses, and the different factors that define the incidence and severity of disease who are frequently situated in the age group young/adult with a social harm and functional non-negligible. This review also contains diagnostic elements and neuropathological features typical of this infection and a brief summary of vaccination against TBE.     

Neuraxial Morphine May Trigger Transient Motor Dysfunction after a Noninjurious Interval of Spinal Cord Ischemia: A Clinical and Experimental Study

Background: A patient underwent repair of a thoracoabdominal aortic aneurysm. Epidural morphine, 4 mg, was given for pain relief. After anesthesia, the patient displayed lower extremity paraparesis. This effect was reversed by naloxone. The authors sought to confirm these observations using a rat spinal ischemia model to define the effects of intrathecal morphine administered at various times after reflow on behavior and spinal histopathology.

Methods: Spinal cord ischemia was induced for 6 min using an intraaortic balloon. Morphine or saline, 30 [mu]g, was injected intrathecally at 0.5, 2, or 24 h after reflow. In a separate group, spinal cord temperature was decreased to 27[degrees]C before ischemia. After ischemia, recovery of motor function was assessed periodically using the motor deficit index (0 = complete recovery; 6 = complete paraplegia).

Results: After ischemia, all rats showed near-complete recovery of function by 4-6 h. Intrathecal injection of morphine at 0.5 or 2 h of reflow (but not at 24 h) but not saline caused a development of hind limb dysfunction and lasted for 4.5 h (motor deficit index score = 4-6). This effect was reversed by intrathecal naloxone (30 [mu]g). Intrathecal morphine administered after hypothermic ischemia was without effect. Histopathological analysis in animals that received intrathecal morphine at 0.5 or 2 h after ischemia (but not at 24 h) revealed dark-staining [alpha] motoneurons and interneurons. Intrathecal saline or spinal hypothermia plus morphine was without effect.     

Mu and delta, but not kappa, opioid agonists induce spastic paraparesis after a short period of spinal cord ischaemia in rats

Background. Intrathecal (IT) morphine given after a short intervalof aortic occlusion in a rodent model induced transient spasticparaparesis via opioid receptor-predicted actions in spinalcord. To determine the role(s) of spinal opioid receptor subtypeswe investigated whether IT administration of various selectiveopioid receptor agonists can induce paraparesis following ashort period of spinal cord ischaemia in rats. Methods. In Sprague–Dawley rats implanted with an IT catheter,spinal cord ischaemia was induced for 6 min using an intraaorticballoon. Mu ([D-Ala², N-Me Phe⁴, Gly-ol⁵] enkephalin), kappa(U50488H) or delta ([D-Pen^2,5] enkephalin) selective agonistswere injected intrathecally 30 min after reperfusion. A separategroup of animals was used to investigate the dose–responseeffect on this motor dysfunction. For this purpose, three dosesof mu, kappa, or delta agonists were injected intrathecallyafter ischaemia. After IT injection, recovery of motor functionwas assessed periodically using the motor deficit index (0=completerecovery; 6=complete paraplegia). Results. IT administration of mu and delta but not kappa agonistsproduced dose-dependent effects in the induction of spasticparaparesis. In addition, this spasticity induced by IT mu anddelta agonists was reversed completely by IT naloxone and naltrindole,respectively. Conclusion. These results suggest that the effect of variousopioids on motor function after a short period of spinal cordischaemia depends upon individual opioid receptor subtypes.      

Total content of RNA in individual nerve cells of spinal ganglion during ischemia in dogs

The total RNA content in the individual nerve cells of the lumbal spinal ganglia in the dog after the 80 minutes lasting partial ischemia was followed. The spinal ganglion neurons did not react in ischemia in the same way. The total RNA content in the individual neurons of the control animals occurred in the range 132-990 arbitrary units, after the ischemia in the range 116-670 arbitrary units. In both groups the cells with the low or high RNA content were seen. The decreases in total RNA content after ischemia was at the higher level of the statistical significance in the group with the largest and middle large neurons giving the evidence about the greater sensitivity to the oxygen shortage in comparison with the group of the smallest spinal ganglion nerve cells.     

Characterization of spinal amino acid release and touch-evoked allodynia produced by spinal glycine or GABA(A) receptor antagonist

Intrathecal strychnine (glycine antagonist) or bicuculline (GABA(A) antagonist) yields a touch-evoked agitation that is blocked by N-methyl-D-aspartate receptor antagonism. We examined the effects of intrathecal strychnine and bicuculline on touch-evoked agitation and the spinal release of amino acids. Fifty-two Sprague-Dawley rats were prepared under halothane anesthesia with a lumbar intrathecal catheter and a loop dialysis catheter. Four days after implantation, rats were randomized to receive an intrathecal injection of N-methyl-D-aspartate (3 microg), strychnine (3 microg) or bicuculline (10 microg), or a combination of N-methyl-D-aspartate with bicuculline or strychnine. The agitation produced by brief light tactile stroking of the flank (tactile allodynia), and the spontaneous spinal release of glutamate, taurine and serine was measured. Intrathecal N-methyl-D-aspartate, strychnine and bicuculline produced similar touch-evoked allodynia. Intrathecal bicuculline and N-methyl-D-aspartate alone evoked a transient spinal release of glutamate and taurine, but not serine, in the 0- 10 min sample, while strychnine did not affect spinal transmitter release at any time. As GABA(A) but not glycine receptor inhibition at equi-allodynic doses increases glutamate release, while the allodynia of both is blocked by N-methyl-D-aspartate receptor antagonism, we hypothesize that GABA(A) sites regulate presynaptic glutamate release, while glycine regulates the excitability of neurons postsynaptic to glutamatergic terminals.     

The effect of graded postischemic spinal cord hypothermia on neurological outcome and histopathology after transient spinal ischemia in rat

BACKGROUND: Previous data have shown that postischemic brain hypothermia is protective. The authors evaluated the effect of postischemic spinal hypothermia on neurologic function and spinal histopathologic indices after aortic occlusion in the rat. METHODS: Spinal ischemia was induced by aortic occlusion lasting 10 min. After ischemia, spinal hypothermia was induced using a subcutaneous heat exchanger. Three studies were conducted. In the first study, the intrathecal temperature was decreased to 34, 30, or 27 degrees C for 2 h beginning with initial reperfusion. In the second study, hypothermia (target intrathecal temperature 27 degrees C) was initiated with reflow and maintained for 15 or 120 min. In the third study, the intrathecal temperature was decreased to 27 degrees C for 2 h starting 5, 60, or 120 min after normothermic reperfusion. Animals survived for 2 or 3 days, at which time they were examined and perfusion fixed with 4% paraformaldehyde. RESULTS: Normothermic ischemia followed by normothermic reflow resulted in spastic paraplegia and spinal neuronal degeneration. Immediate postischemic hypothermia (27 degrees C for 2 h) resulted in decreasing motor dysfunction. Incomplete protection was noted at 34 degrees C. Fifteen minutes of immediate cooling (27 degrees C) also provided significant protection. Delay of onset of post-reflow hypothermia (27 degrees C) by 5 min or more failed to provide protection. Histopathologic analysis revealed temperature-dependent suppression of spinal neurodegeneration, with no effect of delayed cooling. CONCLUSIONS: These findings indicate that the immediate period of reperfusion (0-15 min) represents a critical period that ultimately defines the degree of spinal neuronal degeneration. Hypothermia, when initiated during this period, showed significant protection, with the highest efficacy observed at 27 degrees C.     

Cauda equina syndrome

Single or double-level compression of the lumbosacral nerve roots located in the dural sac results in a polyradicular symptomatology clinically diagnosed as cauda equina syndrome. The cauda equina nerve roots provide the sensory and motor innervation of most of the lower extremities, the pelvic floor and the sphincters. Therefore, in a fully developed cauda equina syndrome, multiple signs of sensory disorders may appear. These disorders include low-back pain, saddle anesthesia, bilateral sciatica, then motor weakness of the lower extremities or chronic paraplegia and, bladder dysfunction. Multiple etiologies can cause the cauda equina syndrome. Among them, non-neoplastic compressive etiologies such as herniated lumbosacral discs and spinal stenosis and spinal neoplasms play a significant role in the development of the cauda equina syndrome. Non-compressive etiologies of the cauda equina syndrome include ischemic insults, inflammatory conditions, spinal arachnoiditis and other infectious etiologies. The use of canine, porcine and rat models mimicking the cauda equina syndrome enabled discovery of the effects of the compression on nerve root neural and vascular anatomy, the impairment of impulse propagation and the changes of the neurotransmitters in the spinal cord after compression of cauda equina. The involvement of intrinsic spinal cord neurons in the compression-induced cauda equina syndrome includes anterograde, retrograde and transneuronal degeneration in the lumbosacral segments. Prominent changes of NADPH diaphorase exhibiting, Fos-like immunoreactive and heat shock protein HSP72 were detected in the lumbosacral segments in a short-and long-lasting compression of the cauda equina in the dog. Developments in the diagnosis and treatment of patients with back pain, sciatica and with a herniated lumbar disc are mentioned, including many treatment options available.     

Parkinson’s disease and cerebrovascular disease: is there a link? A neurosonological case–control study

Cerebrovascular disease (CVD) and idiopathic Parkinson’s disease (PD) frequently occur in the elderly; however, CVD is not frequent in the PD population. The possible relationship between PD and CVD was studied with controversial findings. More specifically, it is unclear whether PD can be protective against the development of vascular disease. To assess the neurosonological examination of a group of PD patients matched with a control group of patients not affected by PD along with the potential risk of developing CVD in the PD group to evaluate any differences. The analysis of the left common carotid artery (CCA) revealed a mean intima-media thickness (IMT) of 0.77 ± 0.21 mm in the PD group and 0.83 ± 0.17 mm in the control group, while the right CCA mean IMT was 0.61 ± 0.17 mm in the PD patients and 0.98 ± 0.18 mm in the control group. The difference was statistically significant in both sides. PD patients show a lower IMT value in older age (70–80 years) and a reduced cardiovascular risk.