Tacrolimus and Cyclosporine A Are of No Benefit to Young Rats with Kaolin-Induced Hydrocephalus

Khan, Osaama H.; Enno, Terry L.; Bigio, Marc R. Del

doi:10.1159/000075259

Cited by 9 publications

(6 citation statements)

References 27 publications

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“…Based on prior reports of axon protection in traumatic brain injury models, we treated 3-week-old hydrocephalic rats with tacrolimus, cyclosporine A, or calpain inhibitor I; there was no statistically significant protection in regard to behavior, brain structure or brain composition in any of the experiments [ 260 ]. In the same model system, we found no evidence for protection using the sodium channel-blocking agents mexiletine and riluzole [ 261 ].…”

Section: Resultsmentioning

confidence: 99%

Nonsurgical therapy for hydrocephalus: a comprehensive and critical review

Bigio

Curzio

2015

Fluids Barriers CNS

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107

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Pharmacological interventions have been tested experimentally and clinically to prevent hydrocephalus and avoid the need for shunting beginning in the 1950s. Clinical trials of varied quality have not demonstrated lasting and convincing protective effects through manipulation of cerebrospinal fluid production, diuresis, blood clot fibrinolysis, or manipulation of fibrosis in the subarachnoid compartment, although there remains some promise in the latter areas. Acetazolamide bolus seems to be useful for predicting shunt response in adults with hydrocephalus. Neuroprotection in the situation of established hydrocephalus has been tested experimentally beginning more recently. Therapies designed to modify blood flow or pulsation, reduce inflammation, reduce oxidative damage, or protect neurons are so far of limited success; more experimental work is needed in these areas. As has been recommended for preclinical studies in stroke and brain trauma, stringent conditions should be met for preclinical studies in hydrocephalus.Electronic supplementary materialThe online version of this article (doi:10.1186/s12987-016-0025-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Nonsurgical therapy for hydrocephalus: a comprehensive and critical review

Bigio

Curzio

2015

Fluids Barriers CNS

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107

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“…Acute hydrocephalic rats showed increased escape latency starting from the second trial block of the single-day MWM task while chronic animals (a different batch of animals, first exposure to the task) took longer to find the underwater platform than their age-matched controls starting in the first trail block of the day. These cannot be attributed to difference in swimming ability between animals ( Figure 1B) (35,70). Neither can it be a consequence of the difference in gross visual ability (70) as our acute hydrocephalic rats performed as good as the age-matched controls during the first block of the trials ( Figure 1C).…”

Section: Functional Implication Of Hydrocephalusinduced Cortical and mentioning

confidence: 91%

Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats

et al. 2016

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Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus.

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“…This increase in latency to find the platform may be explained by the slower swimming speeds of the VM animals reported in this study (Khan et al, 2006). Consistent with a lack of spatial learning changes, these authors were unable to demonstrate MWM deficits when animals were injected with kaolin on P21 (Khan et al, 2003). These kaolin‐treated animals also showed no changes in body weight, locomotor activity, or swimming ability.…”

Section: Introductionmentioning

confidence: 86%

Kaolin‐induced ventriculomegaly at weaning produces long‐term learning, memory, and motor deficits in rats

Williams

Braun

Amos‐Kroohs

et al. 2014

Intl J of Devlp Neuroscience

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Ventriculomegaly occurs when there is imbalance between creation and absorption of cerebrospinal fluid (CSF); even when treated, long-term behavioral changes occur. Kaolin injection in the cisterna magna of rats produces an obstruction of CSF outflow and models one type of hydrocephalus. Previous research with this model shows that neonatal onset has mixed effects on Morris water maze (MWM) and motoric performance; we hypothesized that this might be because the severity of ventricular enlargement was not taken into consideration. In the present experiment, rats were injected with kaolin or saline on postnatal day (P)21 and analyzed in subgroups based on Evan's ratios (ER) of the severity of ventricular enlargement at the end of testing to create 4 subgroups from least to most severe: ER0.4–0.5, ER0.51-0.6, ER0.61-0.7, and ER0.71-0.82, respectively. Locomotor activity (dry land and swimming), acoustic startle with prepulse inhibition (PPI), and MWM performance were tested starting on P28 (122 cm maze) and again on P42 (244 cm maze). Kaolin-treated animals weighed significantly less than controls at all times. Differences in locomotor activity were seen at P42 but not P28. On P28 there was an increase in PPI for all but the least severe kaolin-treated group, but no difference at P42 compared with controls. In the MWM at P28, all kaolin-treated groups had longer path lengths than controls, but comparable swim speeds. With the exception of the least severe group, probe trial performance was worse in the kaolin-treated animals. On P42, only the most severely affected kaolin-treated group showed deficits compared with control animals. This group showed no MWM learning and no memory for the platform position during probe trial testing. Swim speed was unaffected, indicating motor deficits were not responsible for impaired learning and memory. These findings indicate that kaolin-induced ventriculomegaly in rats interferes with cognition regardless of the final enlargement of the cerebral ventricles, but final size critically determines whether lasting locomotor, learning, and memory impairments occur.

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Tacrolimus and Cyclosporine A Are of No Benefit to Young Rats with Kaolin-Induced Hydrocephalus

Cited by 9 publications

References 27 publications

Nonsurgical therapy for hydrocephalus: a comprehensive and critical review

Nonsurgical therapy for hydrocephalus: a comprehensive and critical review

Hydrocephalus compacted cortex and hippocampus and altered their output neurons in association with spatial learning and memory deficits in rats

Kaolin‐induced ventriculomegaly at weaning produces long‐term learning, memory, and motor deficits in rats

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