Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage

About 50% of humans with aneurysmal subarachnoid hemorrhage (SAH) die and many survivors have neurological and neurobehavioral dysfunction. Animal studies usually focused on cerebral vasospasm and sometimes neuronal injury. The difference in endpoints may contribute to lack of translation of treatments effective in animals to humans. We reviewed prior animal studies of SAH to determine what neurological and neurobehavioral endpoints had been used, whether they differentiated between appropriate controls and animals with SAH, whether treatment effects were reported and whether they correlated with vasospasm. Only a few studies in rats examined learning and memory. It is concluded that more studies are needed to fully characterize neurobehavioral performance in animals with SAH and assess effects of treatment

Presynaptic hyperexcitability at cerebellar synapses in traumatic injury rat

Neurotransmission in rat cerebellum following fluid percussion injury (FPI) was studied by extracellular recording method. An increased amplitude of population spikes from presynaptic mossy fibers was detected at 3 days after FPI. However, there were no differences at 1 h, 1 day, 1 week or 2 weeks after FPI compared to naïve controls. An enhanced amplitude of the population spikes, as well as the after hyperpolarization component from presynaptic response of the parallel fibers, was seen in the groups at 3 days and 1 week post FPI, but not in other groups. These results indicate a presynaptic hyperexcitation was induced by FPI within a specific time window. This hyperexcitability may contribute to the reported loss of Purkinje cells after FPI. © 2002 Elsevier Science Ireland Ltd. All rights reserved

Long-term potentiation of evoked presynaptic response at CA3-CA1 synapses by transient oxygen-glucose deprivation in rat brain slices

Physiological activity-dependent long-term changes in synaptic transmission, as long-term potentiation (LTP) are thought to be the substrate of learning and memory. However, a form of postsynaptic pathological LTP at the CA3-CA1 synapses has been demonstrated following few minutes of anoxia and aglycemia in vitro. The ischemia LTP shared many molecular mechanisms with the physiological LTP, and was believed to be involved in the delayed neuronal death following ischemia. However, the role of the presynaptic component in this regard is not known. Here we show that a short period of oxygen-glucose deprivation can induce a form of LTP (lasting for hours) of the presynaptic response at the CA3-CA1 synapses. This form of LTP is independent of postsynaptic α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors, but Ca dependent. This presynaptic LTP may represent a presynaptic hyperexcitability of the afferent fibers following ischemia, and responsible for the excitotoxicity to the CA1 neurons (ischemia-induced increases of glutamate release that kills neurons) and the postsynaptic pathological ischemic LTP. © Springer-Verlag 2005. 2

Presynaptic excitability as a potential target for the treatment of the traumatic cerebellum

Using an extracellular recording method, we have previously shown a hyperexcitability of the presynaptic response in fluid percussion injury (FPI) in rats. In this study, we demonstrated that treatment with cis-ACBD, a glutamate reuptake inhibitor, depressed the presynaptic potential (PSP) in naive/sham controls, while it potentiated the PSP in FPI rats. On the contrary, (RS)-APICA, a selective group II metabotropic glutamate receptor antagonist, potentiated PSP in controls, but depressed PSP in FPI rats. These results indicate that an alteration of the normal function of metabotropic glutamate receptors and glutamate reuptake system or an altered reactivity of presynaptic fibers was induced by FPI. This alteration may contribute to the reported loss of Purkinje cells after FPI. PSP may be used as a potential tool for evaluating treatments of FPI or as a potential target for the prevention of Purkinje cell death. Copyright © 2004 S. Karger AG, Basel

Presynaptic excitability as a potential target for the treatment of the traumatic cerebellum

Using an extracellular recording method, we have previously shown a hyperexcitability of the presynaptic response in fluid percussion injury (FPI) in rats. In this study, we demonstrated that treatment with cis-ACBD, a glutamate reuptake inhibitor, depressed the presynaptic potential (PSP) in naive/sham controls, while it potentiated the PSP in FPI rats. On the contrary, (RS)-APICA, a selective group II metabotropic glutamate receptor antagonist, potentiated PSP in controls, but depressed PSP in FPI rats. These results indicate that an alteration of the normal function of metabotropic glutamate receptors and glutamate reuptake system or an altered reactivity of presynaptic fibers was induced by FPI. This alteration may contribute to the reported loss of Purkinje cells after FPI. PSP may be used as a potential tool for evaluating treatments of FPI or as a potential target for the prevention of Purkinje cell death. Copyright © 2004 S. Karger AG, Basel

Honokiol and magnolol selectively interact with GABA\u3csub\u3eA\u3c/sub\u3e receptor subtypes in vitro

Honokiol and magnolol have been identified as modulators of the GABA receptors in vitro. Our previous study suggested a possible selectivity of honokiol and magnolol on GABA receptor subtypes. This possibility was examined in the current study by H-muscimol and H-flunitrazepam binding assays on various rat brain membrane preparations and human recombinant GABA receptor subunit combinations expressed by the Sf-9/baculovirus system. Generally, honokiol and magnolol have a similar enhancing effect on H-muscimol binding to various membrane preparations in nonsaturation binding assays. Honokiol and magnolol preferentially increased H-muscimol binding to hippocampus compared to cortex and cerebellum (with a maximum enhancement of 400% of control). As for subunit combinations, honokiol and magnolol have a more potent enhancing effect on α subunit containing combinations (with a maximum enhancement of 400-450% of control). This action was independent of the γ subunit. In saturation binding assays, magnolol affected either the number of binding sites (ca. 4-fold on α containing combinations) or the binding affinity (on α containing combinations) of H-muscimol binding to various GABA receptor subunit combinations. In contrast, honokiol increased only binding sites on α β γ and α β combinations, but both the number of binding sites and the binding affinity on α β γ and α β combinations. These results indicate that honokiol and magnolol have some selectivity on different GABA receptor subtypes. The property of interacting with GABA receptors and their selectivity could be responsible for the reported in vivo effects of these two compounds. Copyright © 2001 S. Karger AG, Basel. A A A 2 2 1 A 2 3 2s 2 3 1 2 2S 1 2 A A 3 3 3 3

Developing a model of chronic subdural hematoma

Chronic subdural hematoma (CSDH) is a common neurosurgical condition that has a high incidence in the increasing elderly population of many countries. Pathologically, it is defined as a persistent liquefied hematoma in the subdural space more than 3 weeks old that is generally encased by a membraneous capsule. CSDHs likely originate after minor head trauma, with a key factor in its development being the potential for a subdural cavity to permit its expansion within, which is usually due to craniocerebral disproportion. The pathogenesis of CSDH has been attributed to osmotic or oncotic pressure differences, although measurements of these factors in the CSDH fluid do not support this theory. Current belief is that CSDH arises from recurrent bleeding in the subdural space, caused by a cycle of local angiogenesis, inflammation, coagulation and ongoing fibrinolysis. However, because of a lack of detailed knowledge about the precise mechanisms, treatment is often limited to surgical interventions that are invasive and often prone to recurrence. Thus, it is possible that an easily reproducible and representative animal model of CSDH would facilitate research in the pathogenesis of CSDH and aid with development of treatment options. © 2011 Springer-Verlag/Wien