Elsevier

Brain, Behavior, and Immunity

Volume 87, July 2020, Pages 645-659
Brain, Behavior, and Immunity

AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

https://doi.org/10.1016/j.bbi.2020.02.009Get rights and content
Under a Creative Commons license
open access

Highlights

  • Animals bearing malignant glioma suffer from cognitive deficiency.

  • Tumour associated inflammation can lead to cognitive impairment.

  • AVNP2 alleviated tumour associated inflammation in rat model of C6 glioma.

  • AVNP2 showed protective effect on cognitive decline induced by C6 glioma in rats.

  • THz technology can help to identify the margin of brain tumour.

Abstract

Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1β, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.

Abbreviations

NPs
nanoparticles
AVNPs
antiviral-nanoparticles
AMNPs
antimicrobial nanoparticles
SARS
severe acute respiratory syndrome
MRSA
methicillin-resistant staphylococcus aureus
LTP
long-term potentiation
PSD-95
postsynaptic density-95
SYP
synaptophysin
IL-1β
interleukin-1β
IL-6
interleukin-6
TNF-α
tumour necrosis factor-α
ELISA
enzyme linked immunosorbent assay
WB
western blot
VEGF
vascular endothelial growth factor
BDNF
brain derived neurotrophic factor
NF-ĸB
nuclear factor kappa-light-chain-enhancer of activated B cells
iNOS
inducible nitric oxide synthase
COX-2
cyclooxygenase-2
GBM
glioblastoma
TAMs
tumour associated macrophages
TME
tumour micro-environment
THz
terahertz
ATR
attenuated total reflection
DMEM
Dulbecco’s modified Eagle’s medium
PBS
phosphate buffered saline
XPS
X-ray photoelectron spectroscope
FTIR
Fourier transform infrared spectroscopy
SD
Sprague-Dawley
NS
normal saline
NOFT
novel object recognition test
RI
recognition index
DI
discrimination index
T1
time 1
T2
time 2
OFT
open field test
CA1
cornu ammonis 1
TBS
theta burst stimulation
DPX
distyrene, plasticizer and xylene
BCA
bicinchoninic acid
SDS-PAGE
sodium dodecyl sulfate polyacrylamide gel electrophoresis
PDVF
polyvinylidene fluoride
TBST
tris buffered saline tween
RT
room temperature
DAPI
4,6-diamidino-2-phenylindole
SEM
standard error of the mean
ANOVA
analysis of variance
fEPSPs
field excitatory postsynaptic potentials
LSD analysis
least significant difference
ECs
endothelial cells
AD
Alzheimer disease

Keywords

C6 glioma
AVNP2
Cognitive function
Inflammation

Cited by (0)

1

J. Li, and M. Liu equally contributed to this study.