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Objective To investigate the effect of bone window closure on moderate to severe traumatic brain injury (TBI) in mice by controlled cortical impact (CCI). Methods A total of 200 healthy male mice were divided into 2 groups for moderate and severe TBI. Fifty were randomly selected from each group for bone window closed, and the remaining 50 were not closed. The intracranial pressure (ICP) was monitored, the water content of brain tissue and the volume of cerebral edema were measured, the degree of neurological impairment was assessed by modified Neurological Severity Score (mNSS), and the spatial learning ability and memory were evaluated by Morris water maze test. Nissl staining assessed the degree of neuronal damage in the cerebral cortex and CA1 region of the hippocampus. Results For ICP, there were differences in ICP between the bone window closed group and the unclosed group in both the moderate and severe TBI (P = 0.007, 0.000). There were also significant differences in ICP at different observation time points after modeling (P = 0.000, 0.000). The ICP on 1 d of the moderate bone window closed group was higher than that in the moderate bone window unclosed group (P = 0.009), 1 d (P = 0.000) and 3 d (P = 0.038) of the severe bone window closed group was higher than that of the severe bone window unclosed group. On 7 d, the ICP in the moderate bone window closed group (P = 0.000, 0.000) and the severe bone window closed group (P = 0.000, 0.008) was lower than that on 1 and 3 d, and the ICP on 3 d was also lower than that on 1 d (P = 0.000, 0.000). The ICP in the moderate bone window unclosed group on 7 d was lower than that on 1 d (P = 0.031). The water content of brain tissue was lower on 1 d (P = 0.028), 3 d (P = 0.023) and 7 d (P = 0.023) in severe bone window closed group than that of severe bone window unclosed group. The volume of brain edema in the bone window closed group was smaller than that in the bone window unclosed group (P = 0.021, 0.037). In the evaluation of the degree of neurological impairment, there were differences in mNSS scores at different observation time points between the bone window closed group and the bone window unclosed group (P = 0.000, 0.001). On 7 d, the mNSS scores of the moderate bone window closed group (P = 0.002), the moderate bone window unclosed group (P = 0.013) and the severe bone window closed group (P = 0.009) were all lower than those on 1 d. The mNSS scores of the severe bone window closed group (P = 0.006) and the severe bone window unclosed group (P = 0.002) were all lower than those of 3 d. Morris water maze test showed that the platform latency of mice in the severe bone window closed group was longer than that in the severe bone window unclosed group (P = 0.045), and the target quadrant residence time was shorter than that in the severe bone window unclosed group (P = 0.025). Nissl staining showed compared with the moderate bone window unclosed group, the density of Nissl bodies in cerebral cortex neurons was decreased, the staining was lighter, and the density of Nissl bodies in cerebral cortex neurons of CA1 region of hippocampus was decreased, the Nissl staining was lighter and the shape was blurred in the moderate bone window closed group. In severe TBI model mice, compared with the bone window unclosed group, the density of Nissl bodies in cerebral cortex and hippocampal CA1 region of the bone window closed group was decreased, the staining was blurred, and more metachromic particles appeared, hippocampal CA1 region body edema, the Nissl staining blurred. Conclusions In moderate TBI model mice, bone window closure increases ICP in the acute stage, but has no significant effect on the degree of cerebral edema, neurological function and cognitive function. In severe TBI model mice, bone window closure can lead to increased ICP and decreased spatial learning ability and memory, but it can reduce the degree of brain edema and improve neurological function. It is suggested that bone window closure should be selected according to the purpose of the study.

To display the capability of the phenolic acid nutraceutical ferulic acid (FLA) in optimizing the in vitro/in vivo properties of the antiviral drug amantadine hydrochloride (AMH) and achieve synergistically enhanced antiviral effects, thereby gaining some new insights into pharmaceutical cocrystals of antiviral drugs with phenolic acid nutraceuticals, a cocrystallization strategy of dual optimization was created. Based on this strategy, the first drug-phenolic acid nutraceutical cocrystal of AMH with FLA, namely AMH-FLA-H2O, was successfully assembled and completely characterized by employing single-crystal X-ray diffraction and other analytical techniques. The cocrystal was revealed to be composed of AMH, FLA, and water molecules in the ratio of 3 : 1 : 1.5, and charge-assisted hydrogen bonds containing chloride ions crucially maintained the crystal lattice together with water molecules. The in vitro/in vivo properties of the cocrystal were systematically evaluated via both theoretical and experimental methods, and the results indicate that the dissolubility of AMH is down-regulated by two-thirds in the cocrystal, resulting in its potential for sustained pharmacokinetic release and the elimination of the adverse effects of AMH. More importantly, the enhanced antiviral effects of the current cocrystal were proven against four viral strains, and the pharmaceutical synergy between AMH and FLA was realized with a combination index (CI) of less than 1. Thus, the present work provides a novel crystalline product with bright commercial prospect for the classical antiviral drug AMH and also establishes an avenue for the synergetic antiviral application of nutraceutical phenolic acids via the cocrystallization strategy of dual optimization. [ABSTRACT FROM AUTHOR]

Correction for 'Supramolecular self-assembly of amantadine hydrochloride with ferulic acid via dual optimization strategy establishes a precedent of synergistic antiviral drug-phenolic acid nutraceutical cocrystal' by Ling-Yang Wang et al., Analyst, 2021, 146, 3988–3999, https://doi.org/10.1039/D1AN00478F. [ABSTRACT FROM AUTHOR]