Mongolian medicine Wenguanmu ointment treats eczema by inhibiting the CKLF-1/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The main clinical manifestations of eczema include itching, erythema, swelling and pain. Currently, allergies and TH1/TH2 cytokine imbalances are significant causes of eczema. TCM believes that eczema is mainly caused by incongruity between dry and wet. Wenguanmu ointment is a classic Mongolian medicine, which mainly composed of Xanthoceras sorbifolia Bunge, Coptis chinensis Franch and Bezoar. These ingredients can clear heat and dampness, dispel wind and dehumidification, anti-inflammatoryad analgesic. In this study, it was found that Wenguanmu ointment can treat eczema with anti-inflammatory, analgesic and antipruritic. AIM OF THE STUDY: In this study, the content of main components in Wenguanmu ointment was tested. Moreover, the therapeutic effect and mechanism of Wenguanmu ointment on eczema model mice were studied. MATERIALS AND METHODS: Kunming mice (25 ± 2 g) were randomly divided into 6 groups: Control group; Model group; Vehicle group; Wenguanmu ointment group; Compound dexamethasone acetate cream group; Chushizhiyang ointment group. The eczema mouse model was established by DNCB. HPLC and TLC tests were used to determine the content of the main components in Wenguanmu ointment. HE staining was used to assess skin damage in mice. In order to detect the anti-inflammatory effect of Wenguanmu ointment on eczema, The levels of IgE, TNF-α, IFN-γ, COX-2 and IL-4 in serum was measured by ELISA. Genecards and Online Mendelian Inheritance in Man databases were used to analyze potential target gene predictions, and it was speculated that Wenguanmu ointment was associated with NF-κB signaling pathway and chemokine signaling pathway. To detect this inference, RT-qPCR and western blotting were used to detect protein and mRNA levels of CKLF-1, IκB-α, and NF-κB. RESULTS: Wenguanmu ointment can repress the symptoms of eczema caused by 2, 4-dinitrochlorobenzene, and inhibit the level of serum immunoglobulin E. Simultaneously it restrain the elevation of miscellaneous pro-inflammatory cytokines and chemokines, as well as reducing the expression of CKLF-1 and NF-κB protein in the nucleus, and increasing the protein expression of IκB to improve eczema. CONCLUSIONS: The ameliorating effect of Wenguanmu ointment on eczema lesions can play a importment role by inhibiting the CKLF-1/NF-κB pathway.

PC6 electroacupuncture reduces stress-induced autonomic and neuroendocrine responses in rats.

Stress can trigger cardiovascular disease. Both imbalance of autonomic nervous activity and increase of neurohormonal output are core aspects of stress responses and can lead to cardiovascular disease. PC6 as a very important acupoint is used to prevent and treat cardiovascular disease and to improve stress-related activities. We examined the influence of electroacupuncture (EA) at PC6 on stress-induced imbalance of autonomic nervous activity and increase of neurohormonal output. EA at PC6 relieved increased cardiac sympathetic nervous activity and decreased cardiac vagal nervous activity induced by immobilization stress. Also, EA at PC6 reduced immobilization stress-induced increases of plasma norepinephrine (NE) and adrenaline (E) released from sympatho-adrenal-medullary axis. Finally, EA at PC6 reduced immobilization stress-induced increases of corticotropin-releasing hormone (CRH) in paraventricular hypothalamic nucleus and plasma cortisol (CORT) released from hypothalamic-pituitary-adrenal axis. However, EA at tail had no significant effect on the stress-induced autonomic and neuroendocrine responses. The results demonstrate the role of EA at PC6 regulating the autonomic and neuroendocrine responses induced by stress and provide insight into the prevention and treatment of EA at PC6 for stress-induced cardiovascular disease by targeting autonomic and neuroendocrine systems.

[Effect of inhalation of different-concentrations of moxa smoke on apoptosis and regeneration of olfactory epithelial cells in rats].

OBJECTIVE: To observe the effect of long-term inhalation of moxa-smoke on olfactory epithelial cells in rats, in order to explore the safety of moxa-smoke inhalation (MSI). METHODS: A total of 32 SD rats (half male and half female) were randomly divided into 4 groups: normal, low concentration (LCMSI), medium concentration (MCMSI) and high concentration (HCMSI), with 8 rats in each group. Rats of the LCMSI, MCMSI and HCMSI groups were put into closed boxes which were filled with ignited moxa stick-released smoke at concentrations of (0.11±0.05)mg/m3, (0.23±0.05) mg/m3 and (0.53±0.05)mg/m3, respectively. The treatment was given 4 h each time, twice a day for 90 days. Rats of the normal group were fed routinely. The rats' general state and behavior (including fur appearance, activities in cage, response to external stimuli, spirit, stool, diet and water drinking) were recorded, and the olfactory function was assessed by using latency of finding the buried food pellet (BFP) test. The number of apoptotic olfactory epithelial cells was counted after terminal labeling (TUNEL), and the proliferation of basal cells of the nasal mucosa was detected by BrdU incorporation immunohistochemical technique. RESULTS: The latency of BFP was significantly longer in the MCMSI and HCMSI groups than in the normal and LCMSI groups (P<0.01), and had no significant differences between the LCMSI and normal groups, and between the MCMSI and HCMSI groups (P>0.05). The numbers of the apoptotic olfactory epithelial cells and proliferative basal cell in the nasal mucus tissue were markedly more in the LCMSI, MCMSI and HCMSI groups than in the normal group (P<0.01, P<0.05), and obviously more in the MCMSI and HCMSI groups than in the LMCMSI group (P<0.01), and apparently more in the HCMSI group than in the MCMSI group (P<0.01). The general state observation showed that in the first 45 days, only yellowish fur and water intake increase were seen in rats of the 3 moxa smoke inhalation groups, while no obvious changes in rats of the LCMSI group, and decrease in activities, being sensitive to external stimulation and fiddle-footed, and lower spirit in rats of the MCMSI and HCMSI groups in comparison with rats of the normal group after 90 day's MSI. CONCLUSION: Long-term inhalation of medium and high concentrations of moxa smoke may cause a reduction of the olfactory sensitivity and an increase of apoptosis of olfactory epithelial cells and proliferation of basal cells.

[Effect of different concentrations of moxa smoke exposure on nasal mucosal injury and expression of serum IL-1, IL-6 and TNF-α in rats].

OBJECTIVE: To observe the effect of long-term moxa smoke exposure of different concentrations on olfactory function in rats, and provide experimental basis of safety study of moxa smoke produced by moxibustion. METHODS: Forty SD rats were randomly divided into a normal control group, a low-concentration moxa smoke group, a moderate-concentration moxa smoke group and a high-concentration moxa smoke group, 10 rats in each one. The rats in the moxa smoke groups were put into three plexiglass moxibustion boxes with different moxa smoke concentrations, 4 hours per times, twice a day for 90 days. The general state of rats was evaluated before and during the experiment. After the intervention, the olfactory function was evaluated by two-bottle experiment (TBE); the morphology of nasal mucosa was observed by HE staining; the apoptosis of olfactory epithelial cells in nasal mucosa was detected by TUNEL method; the serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by ELISA method. RESULTS: In the late stage of moxa smoke exposure (45-90 days into intervention), the behavioral activity of rats in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was weaker than that in the normal control group, and their response to stimulation was strong, and their mental state was worse. After intervention, the drinking rate of vinegar-water mixture in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was higher than that in the normal control group and the low-concentration moxa smoke group (P<0.01). The hierarchical structure of nasal mucosa in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was unclear, disordered, necrotic and inflammatory cell infiltration was serious; the number of apoptotic cells in olfactory epithelium of nasal mucosa in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group was more than that in the normal control group and the low-concentration moxa smoke group (P<0.01), that in the high-concentration moxa smoke group was more than the moderate-concentration group (P<0.01). The serum levels of IL-1, IL-6 and TNF-α in the low-concentration moxa smoke group, the moderate-concentration moxa smoke group and the high-concentration moxa smoke group were higher than the normal control group (P<0.01), and those in the moderate-concentration moxa smoke group and the high-concentration moxa smoke group were higher than the low-concentration moxa smoke group (P<0.01), and those in the high-concentration moxa smoke group were higher than moderate-concentration moxa smoke group (P<0.01). CONCLUSION: The long-term exposure to low, moderate and high concentrations of moxa smoke could cause pathological changes in nasal mucosa and increase the serum levels of IL-1, IL-6 and TNF-α; the moderate and high concentrations of moxa smoke exposure could cause a series of damage to olfactory function and reduce olfactory sensitivity in rats.

Melatonin ameliorates microvessel abnormalities in the cerebral cortex and hippocampus in a rat model of Alzheimer's disease.

Melatonin can attenuate cardiac microvascular ischemia/reperfusion injury, but it remains unclear whether melatonin can also ameliorate cerebral microvascular abnormalities. Rat models of Alzheimer's disease were established by six intracerebroventricular injections of amyloid-beta 1-42, administered once every other day. Melatonin (30 mg/kg) was intraperitoneally administered for 13 successive days, with the first dose given 24 hours prior to the first administration of amyloid-beta 1-42. Melatonin ameliorated learning and memory impairments in the Morris water maze test, improved the morphology of microvessels in the cerebral cortex and hippocampus, increased microvessel density, alleviated pathological injuries of cerebral neurons, and decreased the expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2. These findings suggest that melatonin can improve microvessel abnormalities in the cerebral cortex and hippocampus by lowering the expression of vascular endothelial growth factor and its receptors, thereby improving the cognitive function of patients with Alzheimer's disease. This study was approved by the Animal Care and Use Committee of Jinzhou Medical University, China (approval No. 2019015) on December 6, 2018.

Hypoxic Preconditioning Ameliorates Amyloid-ß Pathology and Longterm Cognitive Decline in AßPP/PS1 Transgenic Mice.

BACKGROUND AND OBJECTIVE: Hypoxic Preconditioning (HPC) has been well established to trigger endogenous mechanisms of neuroprotection basing on models of hypoxic and ischemic diseases in the Central Nervous System (CNS). However, its effects against Alzheimer's Disease (AD) still lack substantial evidence and in-depth exploration. The present study aimed to investigate the impacts of HPC on AD-related memory decline and amyloid-ß (Aß) pathology in AßPP/PS1 transgenic mice. METHODS: Seven-week-old AßPP/PS1 transgenic mice were randomized into HPC and non-HPC groups. The HPC groups were treated with early and repetitive HPC for four weeks, while the non-HPC group was raised under normoxia condition. All the animals were then raised until the age of 28 weeks when Morris water maze tests were conducted to examine the animals' spatial memory. Indicators for Aß pathology (soluble Aß levels and numbers of Aß plaques) and the expression of relevant proteins were measured to explore potential mechanisms. RESULTS: The results showed that HPC ameliorated memory decline and Aß pathology in AßPP/PS1 mice. The protein levels of Amyloid-ß Precursor Protein (AßPP) and ß-site APP Cleaving Enzyme 1 (BACE1) were reduced while that of Hypoxic inducible factor 1α (HIF-1α) was elevated in HPC groups. CONCLUSION: HPC might be a promising strategy for AD intervention. Its potential protection might be realized via downregulating the expressions of AßPP and BACE1 and hence inhibiting Aß pathology. Notably, HIF-1α might play a key role in mediating subsequent neuroadaptive changes following HPC.

[Influence of moxibustion with moxa sticks with different diameters and at different distances from surface of "Zusanli"(ST36) on local skin temperature in rats].

OBJECTIVE: To observe the impact of moxa-stick with different diameters and at different distances on skin temperature in local "Zusanli"(ST36) region, so as to select suitable specifications for moxibustion. METHODS: A total of 120 male SD rats were randomly divided into diameters of 0.5, 0.9, 1.2 and 1.8 cm, and distances of 1, 2, 3, 4 and 5 cm groups, with 6 rats in each group. Moxa-stick with different diameters mentioned above was applied to the right ST36 (right hind limb) for 10 min every time at different distances (between the ignited moxa-stick tip and the skin) mentioned above, and the left ST36 was used as the control point. The skin temperature was detected by using an infrared thermometer. RESULTS: After application of moxibustion to ST36 region, the skin temperature was increased gradually along with the increased diameter of moxa-sticks and decreased along with the increased distance from the ignited moxa-stick tip to the skin. There were no significant changes in the skin temperature of the left control acupoint ST36. The skin temperature was below 40 ℃, between 43 to 55 ℃, over 43℃ and between 43 to 61 ℃, when the moxa-stick was 0.5 cm, 0.9 cm, 1.2 cm and 1.8 cm in diameter, and was kept 1, 2, 3 and 3 to 5 cm away from the skin surface, respectively. When the moxa-stick with a diameter of 1.8 cm was kept at a distance of 1 to 2 cm, the skin temperature reached 71 to 93 ℃ to cause obvious local burn lesion. CONCLUSION: During moxibustion, the ignited moxa-sticks with diameters of 0.5, 0.9, 1.2 and 1.8 cm are suitable to be kept less than 1, 1 to 2, 2 to 3, and 3 to 5 cm away from the skin surface of ST36, respectively.

MicroRNA-145 regulates the proliferation, migration and invasion of human primary colon adenocarcinoma cells by targeting MAPK1.

Primary colon adenocarcinoma is responsible for high rates of mortality worldwide. The late diagnosis and lack of reliable biomarkers and therapeutic targets forms a bottleneck in the treatment of colon cancer. In the present study, the therapeutic potential of an important microRNA (miR), namely miR­145, was investigated in primary colon adenocarcinoma cells. The results revealed that the expression of miR­145 was significantly (P<0.05) downregulated in colon adenocarcinoma cells and the ectopic expression of miR­145 in colon cancer inhibited proliferation by promoting the apoptosis of SW480 primary colon adenocarcinoma cells. Furthermore, bioinformatics analysis revealed that miR­145 exerts its effected by targeting mitogen­activated protein kinase (MAPK) in SW480 cells. This was confirmed by expression analysis wherein the expression of MAPK1 was significantly (P<0.05) upregulated in the primary colon adenocarcinoma cells and the ectopic expression of miR­145 inhibited the expression of MAPK1. By contrast, the silencing of MAPK1 had similar effects on the proliferation, migration and invasion of SW480 cells as that of the overexpression of miR­145. Furthermore, it was observed that the inhibition of miR­145 did not reverse the effects of MAPK1 silencing on SW480 cells. However, the overexpression of MAPK1 led to considerable reversal of the effects of the overexpression of miR­145 on the proliferation, migration and invasion of SW480 cells. The effects of the overexpression of miR­145 were also evaluated in vivo in xenografted mice and it was observed that the overexpression of miR­145 also inhibited tumor growth and volume in vivo. Taken together, it was concluded that miR­145 may prove to be an important therapeutic target for colon cancer.

Efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy: a meta-analysis.

BACKGROUND AND PURPOSE: Despite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice. METHODS: Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies of the efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy; the included studies were reviewed. Meta-analyses were performed using STATA to determine combined efficacy rates and combined rates of compliance with the ketogenic diet and its main subtypes. RESULTS: In total, 12 studies qualified for inclusion, and data from 270 patients were evaluated.The results of the meta-analysis revealed combined efficacy rates of all types of ketogenic diet, a classical ketogenic diet, and a modified Atkins diet were 42%, 52%, and 34%, respectively; the corresponding combined compliance rates were 45%, 38%, and 56%. CONCLUSIONS: The results indicate that a ketogenic diet is a promising complementary therapy in adult intractable epilepsy, and that while a classical ketogenic diet may be more effective, adult patients are likely to be less compliant with it than with a modified Atkins diet.

[A real-time determination method with laser measurement for depth profile analysis of GD-OES].

This paper presents the traditional methods of GD depth analysis method and also its limitations, and the earlier studies of real-time depth measurement technology. A new method of real-time depth determination by laser technology for GD-OES depth analysis is proposed. The real-time depth measurement system is composed of laser displacement sensor and new designed Grimm-type GD source based on laser measurement method, and the system design and technical principles are described in detail. Sputtering depth measurement signal and element spectrum signal can be synchronously collected by this system. The displacement phenomenon of glow discharge source during real-time sputtering depth measurement process is analyzed. The real-time sputtering depth measurement curve of zinc alloy standard sample was tested by two laser displacement sensors measurement system. The actual value of sputtering depth was obtained by adding the depth measurement curve of sputtering surface and the reference plane curve, and the actual depth result is in line with Dektak8-type surface profilometer.

[New design of Grimm-type glow discharge source for real-time sputtered depth measurement].

The crater depth value of sample surface during sputtering is important analysis information for the depth profile analysis of glow discharge spectrometry. Real-time sputtered depth measurement with Laser triangulation measurement method for glow discharge compositional analysis, effectively solves the issues of incorrect depth value calculation and complicated procedures in traditional depth analysis method. This paper presents a new Grimm-type glow discharge source for real-time sputtering depth measurement by laser displacement sensor. This GD source also ensures fine sputtering effects and ideal resolution for multi-layer structure and interface. Optical fiber is used to transmit glow spectrum signal from GD-source to multi-channel photoelectric detection system. The design for the first time accomplishes the real-time signal collection and time-based synchronization analysis for both spectrum signal and sputtering depth signal. The real-time sputtering depth measurement curve of standard samples is obtained. The design and operating principle of this new-type GD-source is described in detail. Under the sputtering conditions of 30 mA, 900 V and 20 minutes, the sputtering rates of iron-based and copper-based sample sputtered by this GD source with good depth resolution are about 10 and 55 nm x s(-1). Surface topography picture of sputtering crater and microphotograph of metal samples are provided in the paper. Low-alloy steel standard sample is tested with this new GD source, the relative standard deviation (RSD) of C, Cu, Al, Ni, Mo, Mn and V elements are less than 1.7%, while for Cr and Si elements RSDs are less than 2.6%. The result data of the testing is provided in this paper.

[Automatic adjustment control system for DC glow discharge plasma source].

There are three important parameters in the DC glow discharge process, the discharge current, discharge voltage and argon pressure in discharge source. These parameters influence each other during glow discharge process. This paper presents an automatic control system for DC glow discharge plasma source. This system collects and controls discharge voltage automatically by adjusting discharge source pressure while the discharge current is constant in the glow discharge process. The design concept, circuit principle and control program of this automatic control system are described. The accuracy is improved by this automatic control system with the method of reducing the complex operations and manual control errors. This system enhances the control accuracy of glow discharge voltage, and reduces the time to reach discharge voltage stability. The glow discharge voltage stability test results with automatic control system are provided as well, the accuracy with automatic control system is better than 1% FS which is improved from 4% FS by manual control. Time to reach discharge voltage stability has been shortened to within 30 s by automatic control from more than 90 s by manual control. Standard samples like middle-low alloy steel and tin bronze have been tested by this automatic control system. The concentration analysis precision has been significantly improved. The RSDs of all the test result are better than 3.5%. In middle-low alloy steel standard sample, the RSD range of concentration test result of Ti, Co and Mn elements is reduced from 3.0%-4.3% by manual control to 1.7%-2.4% by automatic control, and that for S and Mo is also reduced from 5.2%-5.9% to 3.3%-3.5%. In tin bronze standard sample, the RSD range of Sn, Zn and Al elements is reduced from 2.6%-4.4% to 1.0%-2.4%, and that for Si, Ni and Fe is reduced from 6.6%-13.9% to 2.6%-3.5%. The test data is also shown in this paper.

[The relationship between the aquaporin-4 and brain edema, pathologic change, ultrastructure in peri-hematoma tissue in patients with intracerebral hemorrhage].

OBJECTIVE: To observe the expression of aquaporin-4 (AQP-4) mRNA and study the relationship between AQP-4, brain edema, pathological changes and ultrastructure of peri-hematoma tissue in intracerebral hemorrhage (ICH) patients. METHODS: Intracranial operation was performed via nonfunctional area with a funnel-like approach on 30 ICH patients. The brain tissue which must be removed 1 cm away the hematoma was removed within 12 hours for observation as normal brain tissue and taken as the control group (7 patients), and which of the brain tissue within 1 cm around hematoma was taken as the study specimens. The experimental group was subdivided into five groups according to the time interval after ICH: <6 hours (6 cases), 6-12 hours (7 cases), 12-24 hours (5 cases), 24-72 hours (6 cases), and >72 hours ( 6 cases ). Expression of the AQP-4 mRNA, brain edema, pathological and ultrastructural changes were observed with reverse transcription-polymerase chain reaction (RT-PCR), light microscope and electron microscope. RESULTS: The expression of the AQP-4 mRNA was not remarkable, the morphology and construction were basically normal in control group. The expression of AQP-4 mRNA was mild (1.17+/-0.41)and there was edema of neuroglia in the <6 hours group. After 6 hours, besides neuroglial edema, the expression of the AQP-4 mRNA was gradually obvious, capillary endothelial cells began to swell too, and tight junctions gradually began to loosen. In the 12-72 hours group the expression of the AQP-4 mRNA reached its peak (3.50+/-0.55, 3.60+/-0.55, both P<0.01), and brain edema was most prominent, and electron microscopy showed that neurons, neuroglia, and capillary endothelial cells were markedly deformed. After 72 hours, the expression of AQP-4 mRNA gradually recovered, and brain cells showed less damage. On the 5th day the damage began to repair, and on the 8th day, the damage was basically repaired. The correlation analysis showed that there was a remarkable positive correlation between the expression of the AQP-4 mRNA and the degree of brain edema and the size of hematoma (r(1)=0.67, P<0.01; r(2)=0.44, P<0.05) . CONCLUSION: Secondary edema and brain damage may correlate with the expression of the AQP-4 mRNA in the peri-hematoma brain edema area. Removal of hematoma will help decrease the AQP-4 mRNA expression and brain edema damage in the early stage.

[Study of relationship between inflammatory response and apoptosis in perihematoma region in patients with intracerebral hemorrhage].

OBJECTIVE: To investigate the relationship between inflammatory response and cell apoptosis in the perihematoma region in patients with intracerebral hemorrhage (ICH). METHODS: Surgical specimens were obtained from the area 1 cm adjacent to the hematoma. Thirty patients with ICH were divided into five groups: 6, 7, 5, 6, 6 patients in surgery<6 hours, 6-12 hours, 12-24 hours, 24-72 hours and >72 hours groups after the onset, respectively. The control group specimens were obtained from the brain tissues distant to the hematoma in the process of craniotomy in the patients of two former groups. Sections were stained with hematoxylin and eosin (HE) for the examination of pathological changes. Immunohistochemistry, terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) and reverse transcription-polymerase chain reaction (RT-PCR) were applied to determine apoptosis cells, Bax and Bcl-x protein and mRNA. RESULTS: The tissues from perihematoma region were almost normal in control group and <6 hours group. They were slightly damaged in 6-12 hours group, became worse in 12-24 hours group and most severe in 24-48 hours group, and they became better latter and were similar to the control group on 8th day. Infiltration of neutrophils, macrophages and lymphocyte appeared gradually at 6-12 hours, and became much more prominent at 12-24 hours (all P<0.01). The reactive gliosis began to appear at 24-72 hours, and enhanced after 72 hours (all P<0.01). The expression of the apoptosis and Bax protein increased gradually after 6 hours, reaching the peak at 12-24 hours (P<0.05 or P<0.01), and decreased gradually later. The changes in the levels of Bax mRNA were similar to that of the result of immunohistochemistry. Although the expression of Bcl-x protein and mRNA seemed to be increased at 12-72 hours, there was no significant difference between groups (P>0.05). The correlation analysis showed that the infiltration of neutrophils, macrophages and lymphocyte was positively correlated to the TUNEL positive cells and expression of Bax protein and mRNA (P<0.05 or P<0.01), and showed no correlation to Bcl-x protein and mRNA (all >0.05). CONCLUSION: There is a close relationship between inflammatory response and apoptosis and tissue damage in the perihematoma area in ICH.